Obesity is an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. Obesity is associated with increased risk of illness, disability, and death.
The branch of medicine that deals with the study and treatment of obesity is known as bariatrics. As obesity has become a major health problem in the United States, bariatrics has become a separate medical and surgical specialty.
Obesity traditionally has been defined as a weight at least 20% above the weight corresponding to the lowest death rate for individuals of a specific height, gender, and age (ideal weight). Twenty to forty percent over ideal weight is considered mildly obese; 40-100% over ideal weight is considered moderately obese; and 100% over ideal weight is considered severely, or morbidly, obese. More recent guidelines for obesity use a measurement called BMI (body mass index) which is the individual's weight multiplied by 703 and then divided by twice the height in inches. BMI of 25.9-29 is considered overweight; BMI over 30 is considered obese. Measurements and comparisons of waist and hip circumference can also provide some information regarding risk factors associated with weight. The higher the ratio, the greater the chance for weight-associated complications. Calipers can be used to measure skin-fold thickness to determine whether tissue is muscle (lean) or adipose tissue (fat).
Much concern has been generated about the increasing incidence of obesity among Americans. Some studies have noted an increase from 12% to 18% occurring between 1991 and 1998. Other studies have actually estimated that a full 50% of all Americans are overweight. The World Health Organization terms obesity a worldwide epidemic, and the diseases which can occur due to obesity are becoming increasingly prevalent.
Excessive weight can result in many serious, potentially life-threatening health problems, including hypertension, Type II diabetes mellitus (non-insulin dependent diabetes), increased risk for coronary disease, increased unexplained heart attack, hyperlipidemia, infertility, and a higher prevalence of colon, prostate, endometrial, and, possibly, breast cancer. Approximately 300,000 deaths a year are attributed to obesity, prompting leaders in public health, such as former Surgeon General C. Everett Koop, M.D., to label obesity "the second leading cause of preventable deaths in the United States."
Causes and symptoms
The mechanism for excessive weight gain is clear—more calories are consumed than the body burns, and the excess calories are stored as fat (adipose) tissue. However, the exact cause is not as clear and likely arises from a complex combination of factors. Genetic factors significantly influence how the body regulates the appetite and the rate at which it turns food into energy (metabolic rate). Studies of adoptees confirm this relationship—the majority of adoptees followed a pattern of weight gain that more closely resembled that of their birth parents than their adoptive parents. A genetic predisposition to weight gain, however, does not automatically mean that a person will be obese. Eating habits and patterns of physical activity also play a significant role in the amount of weight a person gains. Recent studies have indicated that the amount of fat in a person's diet may have a greater impact on weight than the number of calories it contains. Carbohydrates like cereals, breads, fruits, and vegetables and protein (fish, lean meat, turkey breast, skim milk) are converted to fuel almost as soon as they are consumed. Most fat calories are immediately stored in fat cells, which add to the body's weight and girth as they expand and multiply. A sedentary lifestyle, particularly prevalent in affluent societies, such as in the United States, can contribute to weight gain. Psychological factors, such as depression and low self-esteem may, in some cases, also play a role in weight gain.
|Height And Weight Goals|
|Height||Small Frame||Medium Frame||Large Frame|
|5′2″ 5′3″ 5′4″||128-134 lbs. 130-136 132-138||131-141 lbs. 133-143 135-145||138-150 lbs. 140-153 142-153|
|5′5″ 5′6″ 5′7″||134-140 136-142 138-145||137-148 139-151 142-154||144-160 146-164 149-168|
|5′8″ 5′9″ 5′10″||140-148 142-151 144-154||145-157 148-160 151-163||152-172 155-176 158-180|
|5′11″ 6′0″ 6′1″||146-157 159-160 152-164||154-166 157-170 160-174||161-184 164-188 168-192|
|6′2″ 6′3″ 6′4″||155-168 158-172 162-176||164-178 167-182 171-187||172-197 176-202 181-207|
|Height||Small Frame||Medium Frame||Large Frame|
|4′10″ 4′11″ 5′0″||102-111 lbs. 103-113 104-115||109-121 lbs. 111-123 113-126||118-131 lbs. 120-134 112-137|
|5′1″ 5′2″ 5′3″||106-118 108-121 111-124||115-129 118-132 121-135||125-140 128-143 131-147|
|5′4″ 5′5″ 5′6″||114-127 117-130 120-133||124-141 127-141 130-144||137-151 137-155 140-159|
|5′7″ 5′8″ 5′9″||123-136 126-139 129-142||133-147 136-150 139-153||143-163 146-167 149-170|
|5′10″ 5′11″ 6′0″||132-145 135-148 138-151||142-156 145-159 148-162||152-176 155-176 158-179|
At what stage of life a person becomes obese can affect his or her ability to lose weight. In childhood, excess calories are converted into new fat cells (hyperplastic obesity), while excess calories consumed in adulthood only serve to expand existing fat cells (hypertrophic obesity). Since dieting and exercise can only reduce the size of fat cells, not eliminate them, persons who were obese as children can have great difficulty losing weight, since they may have up to five times as many fat cells as someone who became overweight as an adult.
Obesity can also be a side effect of certain disorders and conditions, including:
- Cushing's syndrome, a disorder involving the excessive release of the hormone cortisol
- hypothyroidism, a condition caused by an underactive thyroid gland
- neurologic disturbances, such as damage to the hypothalamus, a structure located deep within the brain that helps regulate appetite
- consumption of such drugs as steroids, antipsychotic medications, or antidepressants
The major symptoms of obesity are excessive weight gain and the presence of large amounts of fatty tissue. Obesity can also give rise to several secondary conditions, including:
- arthritis and other orthopedic problems, such as lower back pain
- adult-onset asthma
- gum disease
- high cholesterol levels
- high blood pressure
- menstrual irregularities or cessation of menstruation (amenorhhea)
- decreased fertility, and pregnancy complications
- shortness of breath that can be incapacitating
- sleep apnea and sleeping disorders
- skin disorders arising from the bacterial breakdown of sweat and cellular material in thick folds of skin or from increased friction between folds
- emotional and social problems
Diagnosis of obesity is made by observation and by comparing the patient's weight to ideal weight charts. Many doctors and obesity researchers refer to the body mass index (BMI), which uses a height-weight relationship to calculate an individual's ideal weight and personal risk of developing obesity-related health problems. Physicians may also obtain direct measurements of an individual's body fat content by using calipers to measure skin-fold thickness at the back of the upper arm and other sites. The most accurate means of measuring body fat content involves immersing a person in water and measuring relative displacement; however, this method is very impractical and is usually only used in scientific studies requiring very specific assessments. Women whose body fat exceeds 30% and men whose body fat exceeds 25% are generally considered obese.
Doctors may also note how a person carries excess weight on his or her body. Studies have shown that this factor may indicate whether or not an individual has a predisposition to develop certain diseases or conditions that may accompany obesity. "Apple-shaped" individuals who store most of their weight around the waist and abdomen are at greater risk for cancer, heart disease, stroke, and diabetes than "pear-shaped" people whose extra pounds settle primarily in their hips and thighs.
Treatment of obesity depends primarily on how overweight a person is and his or her overall health. However, to be successful, any treatment must affect life-long behavioral changes rather than short-term weight loss. "Yo-yo" dieting, in which weight is repeatedly lost and regained, has been shown to increase a person's likelihood of developing fatal health problems than if the weight had been lost gradually or not lost at all. Behavior-focused treatment should concentrate on:
- What and how much a person eats. This aspect may involve keeping a food diary and developing a better understanding of the nutritional value and fat content of foods. It may also involve changing grocery-shopping habits (e.g., buying only what is on a prepared list and only going on a certain day), timing of meals (to prevent feelings of hunger, a person may plan frequent, small meals), and actually slowing down the rate at which a person eats.
- How a person responds to food. This may involve understanding what psychological issues underlie a person's eating habits. For example, one person may binge eat when under stress, while another may always use food as a reward. In recognizing these psychological triggers, an individual can develop alternate coping mechanisms that do not focus on food.
- How they spend their time. Making activity and exercise an integrated part of everyday life is a key to achieving and maintaining weight loss. Starting slowly and building endurance keeps individuals from becoming discouraged. Varying routines and trying new activities also keeps interest high.
For most individuals who are mildly obese, these behavior modifications entail life-style changes they can make independently while being supervised by a family physician. Other mildly obese persons may seek the help of a commercial weight-loss program (e.g., Weight Watchers). The effectiveness of these programs is difficult to assess, since programs vary widely, drop-out rates are high, and few employ members of the medical community. However, programs that emphasize realistic goals, gradual progress, sensible eating, and exercise can be very helpful and are recommended by many doctors. Programs that promise instant weight loss or feature severely restricted diets are not effective and, in some cases, can be dangerous.
For individuals who are moderately obese, medically supervised behavior modification and weight loss are required. While doctors will put most moderately obese patients on a balanced, low-calorie diet (1200-1500 calories a day), they may recommend that certain individuals follow a very-low-calorie liquid protein diet (400-700 calories) for as long as three months. This therapy, however, should not be confused with commercial liquid protein diets or commercial weight-loss shakes and drinks. Doctors tailor these diets to specific patients, monitor patients carefully, and use them for only a short period of time. In addition to reducing the amount and type of calories consumed by the patient, doctors will recommend professional therapists or psychiatrists who can help the individual effectively change his or her behavior in regard to eating.
For individuals who are severely obese, dietary changes and behavior modification may be accompanied by surgery to reduce or bypass portions of the stomach or small intestine. Although obesity surgery is less risky as of 2003 because of recent innovations in equipment and surgical technique, it is still performed only on patients for whom other strategies have failed and whose obesity seriously threatens their health. Other surgical procedures are not recommended, including liposuction, a purely cosmetic procedure in which a suction device is used to remove fat from beneath the skin, and jaw wiring, which can damage gums and teeth and cause painful muscle spasms.
(Illustration by Argosy Inc.)
Other weight-loss medications available with a doctor's prescription include:
- diethylpropion (Tenuate, Tenuate dospan)
- mazindol (Mazanor, Sanorex)
- phendimetrazine (Bontril, Plegine, Prelu-2, X-Trozine)
- phentermine (Adipex-P, Fastin, Ionamin, Oby-trim)
Phenylpropanolamine (Acutrim, Dextarim) is the only nonprescription weight-loss drug approved by the FDA These over-the-counter diet aids can boost weight loss by 5%. Combined with diet and exercise and used only with a doctor's approval, prescription anti-obesity medications enable some patients to lose 10% more weight than they otherwise would. Most patients regain lost weight after discontinuing use of either prescription medications or nonprescription weight-loss products.
Prescription medications or over-the-counter weight-loss products can cause:
- dry mouth
None of them should be used by patients taking monoamine oxidase inhibitors (MAO inhibitors).
Doctors sometimes prescribe fluoxetine (Prozac), an antidepressant that can increase weight loss by about 10%. Weight loss may be temporary and side effects of this medication include diarrhea, fatigue, insomnia, nausea, and thirst. Weight-loss drugs currently being developed or tested include ones that can prevent fat absorption or digestion; reduce the desire for food and prompt the body to burn calories more quickly; and regulate the activity of substances that control eating habits and stimulate overeating.
The Chinese herb ephedra (Ephedra sinica), combined with caffeine, exercise, and a low-fat diet in physician-supervised weight-loss programs, can cause at least a temporary increase in weight loss. However, the large doses of ephedra required to achieve the desired result can also cause:
- heart arrhythmias
- heart attack
- high blood pressure
Ephedra should not be used by anyone with a history of diabetes, heart disease, or thyroid problems. In fact, an article that appeared in the Journal of the American Medical Association in early 2003 advised against the use of ephedra.
Diuretic herbs, which increase urine production, can cause short-term weight loss but cannot help patients achieve lasting weight control. The body responds to heightened urine output by increasing thirst to replace lost fluids, and patients who use diuretics for an extended period of time eventually start retaining water again anyway. In moderate doses, psyllium, a mucilaginous herb available in bulk-forming laxatives like Metamucil, absorbs fluid and makes patients feel as if they have eaten enough. Red peppers and mustard help patients lose weight more quickly by accelerating the metabolic rate. They also make people more thirsty, so they crave water instead of food. Walnuts contain serotonin, the brain chemical that tells the body it has eaten enough. Dandelion (Taraxacum officinale) can raise metabolism and counter a desire for sugary foods.
Acupressure and acupuncture can also suppress food cravings. Visualization and meditation can create and reinforce a positive self-image that enhances the patient's determination to lose weight. By improving physical strength, mental concentration, and emotional serenity, yoga can provide the same benefits. Also, patients who play soft, slow music during meals often find that they eat less food but enjoy it more.
Getting the correct ratios of protein, carbohydrates, and good-quality fats can help in weight loss via enhancement of the metabolism. Support groups that are informed about healthy, nutritious, and balanced diets can offer an individual the support he or she needs to maintain this type of eating regimen.
As many as 85% of dieters who do not exercise on a regular basis regain their lost weight within two years. In five years, the figure rises to 90%. Repeatedly losing and regaining weight (yo yo dieting) encourages the body to store fat and may increase a patient's risk of developing heart disease. The primary factor in achieving and maintaining weight loss is a life-long commitment to regular exercise and sensible eating habits.
Obesity experts suggest that a key to preventing excess weight gain is monitoring fat consumption rather than counting calories, and the National Cholesterol Education Program maintains that only 30% of calories should be derived from fat. Only one-third of those calories should be contained in saturated fats (the kind of fat found in high concentrations in meat, poultry, and dairy products). Because most people eat more than they think they do, keeping a detailed food diary is a useful way to assess eating habits. Eating three balanced, moderate-portion meals a day—with the main meal at mid-day—is a more effective way to prevent obesity than fasting or crash diets. Exercise increases the metabolic rate by creating muscle, which burns more calories than fat. When regular exercise is combined with regular, healthful meals, calories continue to burn at an accelerated rate for several hours. Finally, encouraging healthful habits in children is a key to preventing childhood obesity and the health problems that follow in adulthood.
New directions in obesity treatment
The rapid rise in the incidence of obesity in the United States since 1990 has prompted researchers to look for new treatments. One approach involves the application of antidiabetes drugs to the treatment of obesity. Metformin (Glucophage), a drug that was approved by the Food and Dug Administration (FDA) in 1994 for the treatment of type 2 diabetes, shows promise in treating obesity associated with insulin resistance.
Another field of obesity research is the study of hormones, particularly leptin, which is produced by fat cells in the body, and ghrelin, which is secreted by cells in the lining of the stomach. Both hormones are known to affect appetite and the body's energy balance. Leptin is also related to reproductive function, while ghrelin stimulates the pituitary gland to release growth hormone. Further studies of these two hormones may lead to the development of new medications to control appetite and food intake.
Adipose tissue — Fat tissue.
Appetite suppressant — Drug that decreases feelings of hunger. Most work by increasing levels of serotonin or catecholamine, chemicals in the brain that control appetite.
Bariatrics — The branch of medicine that deals with the prevention and treatment of obesity and related disorders.
Ghrelin — A recently discovered peptide hormone secreted by cells in the lining of the stomach. Ghrelin is important in appetite regulation and maintaining the body's energy balance.
Hyperlipidemia — Abnormally high levels of lipids in blood plasma.
Hyperplastic obesity — Excessive weight gain in childhood, characterized by the creation of new fat cells.
Hypertension — High blood pressure.
Hypertrophic obesity — Excessive weight gain in adulthood, characterized by expansion of already existing fat cells.
Ideal weight — Weight corresponding to the lowest death rate for individuals of a specific height, gender, and age.
Leptin — A protein hormone that affects feeding behavior and hunger in humans. At present it is thought that obesity in humans may result in part from insensitivity to leptin.
A third approach to obesity treatment involves research into the social factors that encourage or reinforce weight gain in humans. Researchers are looking at such issues as the advertising and marketing of food products; media stereotypes of obesity; the development of eating disorders in adolescents and adults; and similar questions.
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American Dietetic Association. (800) 877-1600. www.eatright.org..
American Obesity Association (AOA). 1250 24th Street NW, Suite 300, Washington, DC 20037. (202) 776-7711 or (800) 98-OBESE. www.obesity.org.
American Society for Bariatric Surgery. 7328 West University Avenue, Suite F, Gainesville, FL 32607. (352) 331-4900. www.asbs.org.
American Society of Bariatric Physicians. 5453 East Evans Place, Denver, CO 80222-5234. (303) 770-2526. www.asbp.org.
HCF Nutrition Research Foundation, Inc. P.O. Box 22124, Lexington, KY 40522. (606) 276-3119.
National Institute of Diabetes and Digestive and Kidney Diseases. 31 Center Drive, USC2560, Building 31, Room 9A-04, Bethesda, MD 20892-2560. (301) 496-3583. 〈www.niddk.nih/gov〉.
National Obesity Research Foundation. Temple University, Weiss Hall 867, Philadelphia, PA 19122.
Weight-Control Information Network. 1 Win Way, Bethesda, MD 20896-3665. (301) 951-1120. 〈www.navigator.tufts.edu/special/win.html〉.
An excess of subcutaneous fat in proportion to lean body mass. Excess fat accumulation is associated with increase in the size (hypertrophy) as well as the number (hyperplasia) of adipose tissue cells. Obesity is variously defined in terms of absolute weight, weight:height ratio, distribution of subcutaneous fat, and societal and esthetic norms. Measures of weight in proportion to height include relative weight (RW, body weight divided by median desirable weight for a person of the same height and medium frame according to actuarial tables), body mass index (BMI, kg/m2) and ponderal index (kg/m3). These do not differentiate between excess adiposity and increased lean body mass. In contrast, subscapular and triceps skinfold measurements and determination of the waist:hip ratio help define the regional deposition of fat and differentiate the more medically significant central obesity from peripheral obesity in adults. No single cause can explain all cases of obesity. Ultimately it results from an imbalance between energy intake and energy expenditure. Although faulty eating habits related to failure of normal satiety feedback mechanisms may be responsible for some cases, many obese people neither consume more calories nor eat different proportions of foodstuffs than nonobese persons. Contrary to popular belief, obesity is not caused by disorders of pituitary, thyroid, or adrenal gland metabolism. However, it is often associated with hyperinsulinism and relative insulin resistance. Studies of obese twins strongly suggest the presence of genetic influences on resting metabolic rate, feeding behavior, changes in energy expenditures in response to overfeeding, lipoprotein lipase activity, and basal rate of lipolysis. Environmental factors associated with obesity include socioeconomic status, race, region of residence, season, urban living, and being part of a smaller family. The prevalence of obesity is greater when weight is measured during winter rather than summer. Obesity is much more common in the southeastern U.S., although the northeastern and midwestern states also have high rates, a phenomenon independent of race, population density, and season.
Synonym(s): adiposity (1) , corpulence, corpulency
[L. obesus, pp. of obedo, to eat up, + -ity]
Obesity is a major public health problem and the leading nutritional disorder in the U.S. It is responsible for more than 280,000 deaths annually in this country. A widely accepted definition of obesity is body weight that is 20% or more in excess of ideal weight:height ratio according to actuarial tables. By this definition, 34% of adults in the U.S. are obese. The National Institutes of Health have defined obesity as a BMI of 30 kg/m2 or more, and overweight as a BMI between 25 and 30 kg/m2. By these criteria, two thirds of adults are either overweight or obese. There is strong evidence that the prevalence of obesity is increasing in both children and adults. Increases are particularly striking among African-Americans and Mexican-Americans. More than 80% of black women over the age of 40 are overweight, and 50% are obese. Among factors blamed for the steady increase in the prevalence of obesity are unhealthful eating practices (high-fat diet, overlarge portions) and the decline in physical activity associated with use of automobiles and public transportation instead of walking, labor-saving devices including computers, and passive forms of entertainment and recreation (television, computer games). Despite efforts of public health authorities to educate the public about the dangers of obesity, it is widely viewed as a cosmetic rather than a medical problem. Obesity is an independent risk factor for hypertension, hypercholesterolemia, Type 2 diabetes mellitus, myocardial infarction, certain malignancies (cancer of the colon, rectum, and prostate in men and of the breast, cervix, endometrium, and ovary in women), obstructive sleep apnea, hypoventilation syndrome, osteoarthritis and other orthopedic disorders, infertility, lower extremity venous stasis disease, gastroesophageal reflux disease, and urinary stress incontinence. Lesser degrees of obesity can constitute a significant health hazard in the presence of diabetes mellitus, hypertension, heart disease, or their associated risk factors. Body fat distribution in central (abdominal or male pattern, with an increased waist:hip ratio) versus peripheral (gluteal or female pattern) adipose tissue depots is associated with higher risks of many of these disorders. Obese people are more liable to injury, more difficult to examine by palpation and imaging techniques, and more likely to have unsuccessful outcomes and complications from surgical operations. Not least among the adverse effects of obesity are social stigmatization, poor self-image, and psychological stress. Weight reduction is associated with improvement in most of the health risks of obesity. All treatments for obesity (other than cosmetic surgical procedures in which subcutaneous fat is mechanically removed) require creation of an energy deficit by reducing caloric intake, increasing physical exercise, or both. Basic weight reduction programs involve consumption of a restricted-calorie, low-fat diet and performance of at least 30 minutes of endurance-type physical activity of at least moderate intensity on most and preferably all days of the week. Behavior modification therapy, hypnosis, anorexiant drugs (sympathomimetic agents, sibutramine), the lipase inhibitor orlistat, and surgical procedures to reduce gastric capacity or intestinal absorption of nutrients are useful in selected cases, but the emphasis should be on establishing permanent changes in lifestyle. Weight reduction is not recommended during pregnancy or in patients with osteoporosis, cholelithiasis, severe mental illness including anorexia nervosa, or terminal illness.
Food is a potent natural reward and food intake is a complex process. Reward and gratification associated with food consumption leads to dopamine (DA) production, which in turn activates reward and pleasure centers in the brain. An individual will repeatedly eat a particular food to experience this positive feeling of gratification. This type of repetitive behavior of food intake leads to the activation of brain reward pathways that eventually overrides other signals of satiety and hunger. Thus, a gratification habit through a favorable food leads to overeating and morbid obesity. Overeating and obesity stems from many biological factors engaging both central and peripheral systems in a bi-directional manner involving mood and emotions. Emotional eating and altered mood can also lead to altered food choice and intake leading to overeating and obesity. Research findings from human and animal studies support a two-way link between three concepts, mood, food, and obesity. The focus of this article is to provide an overview of complex nature of food intake where various biological factors link mood, food intake, and brain signaling that engages both peripheral and central nervous system signaling pathways in a bi-directional manner in obesity.
Keywords: mood, depression, anxiety, food, obesity
It is hypothesized that individuals engage in a variety of behaviors to regulate their mood (Morris and Reilly, 1987). Important among mood regulating behaviors is food consumption. The interaction between mood, emotional state, and feeding behaviors is complex and it is hypothesized that individuals regulate their emotions and mood by changing both food choices and quantities. It is also apparent that mood can affect the self-rewarding mechanisms of food consumption (Morris and Reilly, 1987). Specific types of food tend to be preferred under certain psychological conditions due to the influence of foods on the activity of brain reward centers (Figure 1) (Rangel, 2013; Jauch-Chara and Oltmanns, 2014; Weltens et al., 2014). Positive feedback loops can result in enhancement of appetite leading to obesity. Interestingly, highly palatable foods activate the same brain regions of reward and pleasure that are active in drug addiction (Volkow et al., 2012), suggesting a neuronal mechanism of food addiction leading to overeating and obesity (Davis et al., 2011, 2014; Dileone et al., 2012; Volkow et al., 2012; Dagher, 2013; Davis, 2013; Ziauddeen and Fletcher, 2013; Pai et al., 2014; Potenza, 2014). Dopamine, which directly activates reward and pleasure centers, affects both mood and food intake (Cantello et al., 1989; Diehl and Gershon, 1992; Fochtmann and Fink, 1992; Black et al., 2002; Cawley et al., 2013), further supporting the link between psychology and eating behaviors.
Complex two-way relationship linking food intake, mood, and obesity.
Mood disorders are often found in association with abnormal feeding behaviors. For example, depression and anxiety are comorbidities of obesity (Novick et al., 2005; Simon et al., 2006; Kloiber et al., 2007). Impairment in central nervous system (CNS) function has been linked to obesity that in turn impacts mental and physical health (Allison et al., 2009; Talen and Mann, 2009; Duarte et al., 2010). Obese individuals are at increased risk of developing depression (25, 26), and this risk is doubled in the presence of diabetes (Anderson et al., 2001; De Groot et al., 2001; Labad et al., 2010). Depressed mood is also associated with abdominal obesity and poor diet (Roberts et al., 2003; Dong et al., 2004; Simon et al., 2006; Luppino et al., 2010; Zhao et al., 2011; Hamer et al., 2012). A link between obesity and depression has been found in animal models of mood disorders (Lombard, 2000; Pawels and Volterrani, 2008; Dallman et al., 2003, 2005; Singh et al., 2007, 2009, 2011; Dallman, 2010; Chuang et al., 2011; Diz-Chaves, 2011; Maniam and Morris, 2012; Spence and Courbasson, 2012; Akubuiro et al., 2013; Kumar et al., 2013), suggesting that a common signaling pathway may underlie these phenotypes in both humans and animals.
There are numerous articles on the regulation of food intake, obesity, and mood. However, further exploration of the interaction among mood, food, and obesity is much needed. The aim of this review article is to highlight the complex interplay among mood, emotional state, and eating behaviors that influence body weight. This review provides an overview of known biological factors and foods that influence appetite and mood via brain signaling pathways. Specifically discussed are the foods and biological factors, which override the normal physiological requirements of appetite regulation, and how these factors influence in a bi-directional manner emotion, food, food intake, and obesity (Figure 1).
Central nervous system in regulation of mood, food, and obesity
Bi-directional link of food and emotion
In humans, eating behavior is complex and is affected by both mood and emotions (Lyman, 1982; Mehrabian, 1995; Macht, 1999; Macht and Simons, 2000). However, mood and emotions are distinct. Mood is characterized by psychological arousal in the absence of obvious stimuli that can last for several minutes or longer. In contrast, emotions are short-term affective response to reinforcing stimuli. Of all emotions, a study shows that frequent emotions such as, anger and joy have the strongest influence on appetite and food choice (Macht, 1999). Behavior based findings from human studies of questionnaires, field, and clinical studies suggest an integrative five way model that predicts five different aspects of emotional eating. These five aspects include: food choice, food intake, loss of cognitive controls, food modulating emotions, and emotion-congruent modulating eating, see review by Macht (2008). Therefore, depending on the state of negative emotions or distress, emotional eating is triggered where food intake can either increase or decrease within the same individuals (Ouwens et al., 2009). Emotional state has also been connected with addiction (Parylak et al., 2011). Sensory and psychological pathways influence food choice, the quantity, and meal frequency that may not be a part of normal physiological requirement. Many psychosomatic theories of obesity suggests that obese people overeat due to inability to perceive their physiological state, hunger, and satiety and that overeating reduce emotional discomfort and anxiety (Kaplan and Kaplan, 1957; Schachter, 1968; Bruch, 1985). The internal/external theory of obesity predicts that normal eaters alter their food intake to regulate their emotion, while obese people do not (Schachter, 1968; Canetti et al., 2002). Depending on whether an eater is restrained or emotional, stress and negative emotions could be associated with both increased and decreased motivation to eat; and under those circumstances, food choice differs (Herman and Mack, 1975). Thus, emotional distress influences emotional food choice and intake.
Stress and food intake
There is a close interaction between food, mood, and stress (Benton and Donohoe, 1999; Oliver and Wardle, 1999; Gibson, 2006; Dallman, 2010; Bast and Berry, 2014). Stress can affect feeding behavior (Greeno and Wing, 1994; Yau and Potenza, 2013), resulting in either increased or reduced food intake depending on the types of external or psychological stressors (Oliver and Wardle, 1999; Gibson, 2006; Dallman, 2010; Yau and Potenza, 2013). Similarly, chronic stress can lead to either increased consumption of palatable and rewarding foods leading to obesity or a diminished appetite leading to weight loss (Cartwright et al., 2003; Adam and Epel, 2007; Tryon et al., 2013). Furthermore, following exposure to a stressor, studies show that intake of palatable foods reduce signs of stress and anxiety (Pecoraro et al., 2004; La Fleur et al., 2005; Maniam and Morris, 2010, 2012; Ulrich-Lai et al., 2010; Finger et al., 2011, 2012). Interestingly, stress-induced preference for palatable food is often seen in humans (Souquet and Rowland, 1989; Epel et al., 2004; Pecoraro et al., 2004; Christiansen et al., 2011; Gibson, 2012; Merali et al., 2013; Sharma et al., 2013; Sharma and Fulton, 2013; Meye and Adan, 2014; Park et al., 2014; Rho et al., 2014). Notably, this behavior is extended to animals (Dallman et al., 2003, 2005; Cottone et al., 2009). This suggests that a common neurobiological pathway maybe involved in food choice and patterns of eating behavior during stress.
Mood and food intake
Mood states such as anxiety and depression affect food choice and energy metabolism. Overeating and obesity is often associated with depression and anxiety in humans which has also been reported in animal models (Novick et al., 2005; Simon and Von Korff, 2006; Kloiber et al., 2007; Singh et al., 2007, 2009; Akubuiro et al., 2013; Patterson and Abizaid, 2013; Sharma and Fulton, 2013). Both endocrine and metabolic conditions are exacerbated in major depression (Mcelroy et al., 2004; Simon et al., 2006; De Wit et al., 2010; Luppino et al., 2010; Marijnissen et al., 2011). Individuals experiencing depressed moods show preference for and consume palatable “comfort foods” as a mean to alleviate their negative feelings (Macht, 2008). Although on a short-term basis, palatable foods can provide some relief from negative emotions and mood states, chronic consumption of calorically-rich foods ultimately leads to obesity which in turn promotes vulnerability to depression and anxiety (Novick et al., 2005; Simon et al., 2006; Kloiber et al., 2007; Sharma and Fulton, 2013). Conversely, there are findings showing that prolonged high-fat feeding leads to negative emotional states, increased stress sensitivity, and altered basal corticosterone levels (Sharma et al., 2012). Thus, negative emotion impacts food choice and intake that in turns affects mood in a bi-directional manner.
Interestingly, other behaviors of reduced pleasure/reward experience, anxiety-like behavior, and heightened stress-induced hypothalamic pituitary adrenal axis (HPA) activation have been found in mice. Furthermore, after exposure to chronic high-fat diet and then switching to normal chow diet, mice showed craving for sucrose, high-fat foods, and displayed enhanced anxiety-like behavior (Sharma et al., 2012). Similar findings of increased behavioral and physiological signs of depression and anxiety have been reported in humans when switched from a high-fat sugar diet to regular diet (Avena et al., 2008; Teegarden and Bale, 2008; Cottone et al., 2009; Pickering et al., 2009; Iemolo et al., 2012; Sharma et al., 2012; Blasio et al., 2013). All together, these findings suggest that chronic high-fat feeding promotes negative emotional states and potentiates condition for enhanced sensitivity to stress that leads to continuous repetitive cycles of overeating, weight gain, and depressed mood.
Food preference and mood
Hippocrates, father of modern medicine, said: “Let your food be your medicine, and your medicine be your food” (Prasad, 1998). Research from human trials and animal studies have shown that foods directly influence brain neurotransmitter systems which in turn has effects on mood and performance by altering the brain structure, chemistry, and physiology. Mood can also influence our food choices and expectations on the effects of certain foods can influence our sapiens. Some of those foods impacting mood are discussed below and summarized in Table 1 (Spring et al., 1982-1983; Rogers and Lloyd, 1994).
Summary of biological factors and food influencing mood, emotions, food intake, and brain signaling pathways.
Chocolate has a strong effect on mood, generally increasing pleasant feelings and reducing tension (Osman and Sobal, 2006; Parker et al., 2006b; Cartwright et al., 2007; Fletcher et al., 2007). Chocolate contains psychoactive chemicals such as andamines that stimulate the brain and result in good mood (Ottley, 2000). However, negative feelings are also associated with chocolate in some women on weight loss regimes who experience guilt after eating chocolate. The unique taste and feel from chocolate in the mouth leads to chocolate craving due to sensory factors associated with chocolate eating (Macht and Dettmer, 2006; Osman and Sobal, 2006; Parker et al., 2006b; Cartwright et al., 2007; Fletcher et al., 2007).
Caffeine, mostly consumed in the form of coffee and tea, not only has stimulant effects on enhancing alertness, vigilance, and reaction time but also increases anxiety in susceptible individuals (Acquas et al., 2002; Rossi et al., 2010). Caffeine blocks adenosine receptors in the brain and can relieve headaches, drowsiness, and fatigue. Short-term caffeine deprivation in regular users results in withdrawal symptoms (Rogers, 1995).
Omega-3 fatty acids, found in various foods can influence, mood, behavior, neuroticism, and impulse control (Van Strater and Bouvy, 2006; Conklin et al., 2007; Stahl et al., 2008). Omega-3 fatty acids play a role in major depressive disorder, bipolar disorder, schizophrenia, substance abuse, and attention deficit disorder (Young and Martin, 2003; Parker et al., 2006a; Van Strater and Bouvy, 2006; Stahl et al., 2008). Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), both members of the omega-3 fatty acid family, contribute to the fluidity of the cell membrane, and thereby play an important role in brain development and function (Pawels and Volterrani, 2008). Low blood levels of polyunsaturated omega-3 fatty acids are associated with depression, implying a role in mood disorders (Lombard, 2000; Sanchez-Villegas et al., 2007; Antypa et al., 2012; Moranis et al., 2012; Kang and Gleason, 2013; Grosso et al., 2014).
Micronutrients, such as thiamine (vitamin B1), iron, and folic acid, play a role in emotion. Thiamine containing foods influence mood states (Benton et al., 1995). Improved thiamine status increases well-being, sociability, and overall energy levels. Insufficient amounts of thiamine are associated with impaired mood and cognitive functioning (Benton et al., 1997; Benton and Donohoe, 1999).
Iron deficiency represents one of the most common nutritional problems worldwide. Iron deficiency anemia can result in depressed mood, and problems with attention and lethargy (Benton and Donohoe, 1999).
Folic acid plays an important role in the brain. Folic acid deficiency is associated with depressed mood (Coppen and Bolander-Gouaille, 2005; Young, 2007). Psychiatric patients often run the risk of developing folic acid deficiency due to loss of appetite from anticonvulsant drugs that inhibit folic acid absorption (Ottley, 2000). Collectively, these findings suggest foods influence mood.
Mood can influence food preference (Christensen and Brooks, 2006). Choice of eating palatable foods can either lead to comfort feeling or disgust. A good example of behavioral change that is observed after taking a meal is altered mood. A general effect of meal on behavior is observed from animals to humans where hunger leads to irritability and meal intake leads to arousal and alertness. Thus, a search for food is cultivated. Once satiety sets in, sedentary and calm behaviors most likely have positive rather than negative effect on mood (Macht and Simons, 2000; Macht et al., 2003; Macht and Dettmer, 2006; Macht, 2008). A potential internal information route on emotional behavior was first recognized in 2001 where nutrients from gut were relayed to the brain by the vagus nerve affecting emotions (Zagon, 2001). However, the relationship of emotions, physiological arousal, and mood in a given situation is significantly dependent upon on the subject's motivational state (Reid and Hammersley, 1999) and the individual's personality trait of neuroticism that interacts with mood and response to emotional stimuli (Dess and Edelheit, 1998).
The pathogenesis of both mood and metabolic disorders during obesity can be triggered by certain diets (Wallin and Rissanen, 1994; Sanchez-Villegas and Martinez-Gonzalez, 2013). Diets like Western diets that are rich in saturated fat and low in poly-unsaturated and mono-unsaturated fatty acids tend to increase the incidences of depression (Peet et al., 1998). On the other hand, diet like the Mediterranean diet appears to reduce depression (Sanchez-Villegas and Martinez-Gonzalez, 2013; Sanchez-Villegas et al., 2013). Furthermore, many reports show the increased incidence of depression on diets that lack omega-3 polyunsaturated fatty acids (PUFA) and that depression is reduced when intake of PUFA is increased in both humans (Lin and Su, 2007; Sanchez-Villegas et al., 2007; Oddy et al., 2011; Park et al., 2012a) and rodents (Moranis et al., 2012; Park et al., 2012b). Besides mood changes, high fat diets promote increased weight gain, visceral adipose tissue, larger waist circumference, and more cardiovascular disease mortality (Schulze et al., 2006; Molenaar et al., 2009; Romaguera et al., 2009, 2010; Mozaffarian et al., 2011; Estruch and Salas-Salvado, 2013; Nazare et al., 2013). The accumulation of adipose tissue in abdominal stores leads to several complications of obesity including insulin resistance leading to metabolic syndrome (Despres et al., 2006; Tchernof and Despres, 2013). These changes also lead to neurobiological impairments affecting mood disorders such as depression and anxiety (Weber-Hamann et al., 2002; Van Reedt Dortland et al., 2013a,b). It is believed that increased circulating plasma fatty acids such as palmitic acid enters the brain and impairs neurological function (Tsuboi et al., 2013). Palmitic acid impairs leptin and insulin receptor signaling in the hypothalamus and promotes weight gain (Benoit et al., 2009; Kleinridders et al., 2009). Under these circumstances, obesity is promoted, as well as a negative emotional state. In addition, leptin and insulin have been noted to influence mood (Gonder-Frederick La et al., 1989; Lu et al., 2006; Lu, 2007; Zeman et al., 2009; Ryan et al., 2012).
Furthermore, several studies have shown humans on high fat diet manifest mood disorders like depression that correlates positively with high serum palmitate (Tsuboi et al., 2013). Similarly, rats on high fat diet display increased anxiety-like behavior, altered body weight, plasma insulin, leptin, and glucose levels when compared to rats on iso-caloric olive oil high fat diet that show no changes in body weight, glycaemia, leptin, and insulin levels (Hryhorczuk et al., 2013). Thus, saturated fats stimulate HPA disturbances and/or inflammation, leading to anxiogenic-like behavior in animals and depression in humans. All together these findings suggest an association between certain foods and improved mood.
Psychiatric and eating disorders
The Diagnostic and Statistical Manuals of Mental Disorders (DSM-5), which was developed by the American Psychiatric Association in 1994, reported disturbed eating behaviors in psychiatric disorders (American Psychiatric Association, 2013). In humans, melancholic depression is associated with hypercortisolism, anhedonia, hypophagia, and weight loss (Fisher et al., 1997; Krishnan and Nestler, 2008; Ulrich-Lai and Herman, 2009; Hammack et al., 2010; Carroll et al., 2012; Hryhorczuk et al., 2013; Patterson and Abizaid, 2013; Schellekens et al., 2013b). In contrast to atypical depression, the most common forms of depression are characterized by reduced hypothalamic pituitary adrenal axis (HPA) activity, increased appetite, carbohydrate craving, and weight gain (Juruena and Cleare, 2007). Those with abdominal obesity are associated with hyperactive HPA axis due to an elevated response to corticotrophin releasing hormone (CRH) stimulation and increased stimulated response to stress (Pasquali, 2012).
Altered serum cortisol level is associated with depression (Parker et al., 2003; Raison and Miller, 2003; Stetler and Miller, 2011). Altered cortisol, HPA axis, and food intake have been associated with depression (Ulrich-Lai and Herman, 2009; Dallman, 2010; Schellekens et al., 2012a). The neuronal pathways that regulate food intake, and circuitries that act via the HPA axis are implicated in a complex two-way relationship of three concepts between mood, food, and eating behavior (Figure 1) (Kyrou and Tsigos, 2009; Ulrich-Lai and Herman, 2009; Dallman, 2010; Schellekens et al., 2012b, 2013b). It is noted that there is an overlap in neural circuitry of food intake and stress that likely reinforces a link between stress and feeding behavior (Maniam and Morris, 2012). These overlapping circuitries of HPA axis modulating feeding behavior and stress converge on corticosterone hormone producing neurons in the paraventricular nucleus (PVN). Thus, elevated glucocorticoid and a dysfunctional HPA axis are common to both depression and obesity.
Glucocorticoids exert multiple effects on metabolic, endocrine, immune, and behavioral functions. Glucocorticoids regulate reward and emotional processes via their receptors in midbrain and limbic circuits (Arnett et al., 2011; Solomon et al., 2012; Hryhorczuk et al., 2013; Patterson and Abizaid, 2013; Wang et al., 2013). Glucocorticoids not only act peripherally to maintain energy homeostasis but also centrally to modulate HPA activity, emotional, and behavioral effects of stress (Fedoroff et al., 2003; Figueiredo et al., 2003). Under physiologic acute stress, the HPA axis is activated, and glucocorticoids are released. This leads to a major restoration of energy balance by increasing insulin, increasing motivation for palatable food (Piazza and Le Moal, 1997; Dallman et al., 2006; Dallman, 2010), and mobilizing stored energy toward central stores that leads to obesity (Mann and Thakore, 1999). Thus, obesity and mood disorder are linked via the HPA axis. In rodents, chronic corticosterone exposure leads to increased glucocorticoid receptor (GC) expression in fore-brain and basolateral amygdala that results in depressive-like, anxiety-like behaviors, and increased locomotors (Wei et al., 2004; Boyle et al., 2005, 2006). Therefore, these findings suggest that a deficit in glucocorticoid signaling in distinct brain regions may play a role in affective disorder.
Obesity and mood
Obesity increases incidence of anxiety and mood disorders (Simon et al., 2006). Stress induced overeating and obesity is also associated with major depression in humans (Novick et al., 2005; Simon et al., 2006; Kloiber et al., 2007). Individuals under chronic stress tend to have more visceral fat due to excessive systemic cortisol levels (Brown et al., 2004; Adam and Epel, 2007; Kyrou and Tsigos, 2009). In all, there appears to be a good association between hypercortisolemic depression, abdominal fat accumulation (Weber-Hamann et al., 2002), decreased glucocorticoid-mediated negative feed back, and increased corticotropin releasing hormone (CRH) release from the paraventricular nucleus (PVN) (Holsboer, 2000). Furthermore, major depression in adolescence is linked to a higher risk for obesity in adulthood (Richardson et al., 2003). It is also noted that metabolic conditions are exacerbated in depression and vice versa (Mcelroy et al., 2004; Simon et al., 2006; De Wit et al., 2010; Luppino et al., 2010; Marijnissen et al., 2011). Like-wise, stress significantly impacts food intake in both humans and animals, thereby promoting metabolic disturbances (Block et al., 2009; Dallman, 2010; Maniam and Morris, 2012). Overeating can also be considered to be analogous to drugs of use because it reflects an addiction where individuals become physically and psychologically dependent on foods rich in fat and sugar (Avena et al., 2008, 2009; Barry et al., 2009; Parylak et al., 2011; Allen et al., 2012; Davis, 2013). Reports also show that with intake of palatable rewarding food, acute stress responses are reduced (Dallman et al., 2003; Lutter and Elmquist, 2009; Chuang et al., 2011; Kumar et al., 2013), thereby showing the potential of “comfort eating” in stress relief. All together these findings suggest that there is a reciprocal link in mood disorder and obesity.
Rodent models of mood and eating disorders
Rodent studies have provided the best insight into dopamine-mediated food intake. Dopamine deficient mice die quickly due to decreased food intake (Hnasko et al., 2004). Dopamine when given in the striatum rescues deficient food intake by restarting feeding behavior. Further, when dopamine is given to the nucleus accumbens, a food preference for pleasant food vs. non-pleasant food is observed. Altered dopamine receptor expression is also associated with feeding behavior (Clifton et al., 1991; Zeng et al., 2004; Wang et al., 2009) (18). Post-transcriptional modification such as RNA editing could also play a role in altered reward circuitry mediating overeating behavior (18). It is noteworthy that altered serotonin 2C receptor (5HT2CR) editing has been associated with dopamine production, reward, mood, feeding, and recently obesity (Burns et al., 1997; Sodhi et al., 2001; Gurevich et al., 2002; Higgins and Fletcher, 2003; Iwamoto et al., 2005; Rosenzweig-Lipson et al., 2007; Berg et al., 2008; Olaghere Da Silva et al., 2010; Hayes and Greenshaw, 2011; Schellekens et al., 2012a). Intriguingly, both serotonergic and dopaminergic system are altered in transgenic mice with dysregulated RNA editing enzyme, ADAR2 (Singh et al., 2007, 2009, 2011) (18). These transgenic mice show significantly hyperactive brain regions implicated in reward and also behaviorally display goal oriented behavior toward food in a competitive rewarding environment (Akubuiro et al., 2013). Furthermore, altered dopamine receptor expression, food preference for high fat diet are also observed in ADAR2 transgenic mice (Akubuiro et al., 2013). Interestingly, co-morbidities of depression and anxiety behaviors and altered 5HT2CR editing are observed in ADAR2 transgenic mice (Singh et al., 2007, 2009, 2011). Collectively, these results suggest that co-morbidities of affective disorder, overeating, and obesity could be linked via the modified 5HT2CR in ADAR2 transgenic mice. However, more studies are required to provide a better understanding of the post-transcription modification of the 5HT2CR linking to mood, food, and obesity in ADAR2 transgenic mice.
Dysfunctional serotonergic signaling has been associated with mood and obesity (Wurtman and Wurtman, 1989; Benton and Donohoe, 1999; Sodhi et al., 2001; Iwamoto and Kato, 2003; Schmauss, 2003; Kawahara et al., 2008; Morabito et al., 2010; Singh et al., 2011; Schellekens et al., 2012a; Silberberg et al., 2012; Shinozaki et al., 2013). In another rodent model of depression brain derived neurotropic factor (BDNF) was shown to have an antidepressant-like effect (Siuciak et al., 1997). BDNF has been shown to be a neurotropic factor on serotonergic neurons in BDNF heterozygous mice where dysfunctional serotonergic signaling is associated with aggression, hyperphagia, and weight gain is rescued (Lyons et al., 1999). Further exogenous BDNF application enhances serotonin signaling and modifies several behaviors regulated by serotonin feeding, body weight homeostasis, and analgesia (Siuciak et al., 1994; Pelleymounter et al., 1995). Thus, these studies suggest that dysfunctional serotonergic and dopaminergic systems play a critical role in mood, food intake, and obesity.
Psychobiological relationship of brain reward linking hunger, addiction, overeating, and obesity
Continuous overeating can be viewed as an addictive behavior that involve reward circuitry (Davis, 2013). Reward circuitry involved in addiction spans two key brain regions, (1) the prefrontal region and the amygdala and, (2) the limbic system integrating amygdala with hypothalamus and septal nuclei (Elliott et al., 2000; Schultz, 2000, 2002; Tzschentke, 2001; Baxter and Murray, 2002; Rolls et al., 2002; Koob and Volkow, 2010). The neural mechanism of disrupted dopamine signaling pathways being central to overeating and drugs of use and the overwhelming hallmarks of urge to seek and consume, thereby presents an addiction behavior. Another common phenomenon of compulsive intake of drugs and overconsumption of food intake seen in obesity is the loss of control due to impairments in circuits involved in decision making, self control, interoception, and regulation of mood and stress (Volkow et al., 2010).
Two hormones: ghrelin and leptin interact with the hypothalamus to regulate food intake, energy homeostasis, promote satiety, and hunger. Interestingly, both hormones have been implicated in craving behavior, eating disorder, and mood and have also been associated with the reward pathway (Kiefer et al., 2001; Opland et al., 2010; Dickson et al., 2011). Thereby, suggesting that both ghrelin and leptin are linked to mood and food intake.
There are several neurotransmitter systems involved in feeding such as serotonin, dopamine, opioids, and GABA, of which serotonin and dopamine have been the most closely linked to feeding behavior. Dopamine mediates reward specifically the “wanting” or approach behaviors toward a biologically relevant goals more so than “liking” or enjoyment aspect (Berridge, 1996; Davis et al., 2009). Opioids have been implicated more so in the “liking” or the hedonic aspect of reward processing and both neurotransmitter pathways work together in the perception of reward (Davis et al., 2009). The “wanting” behavior toward a biological relevant goal that is mediated by dopamine is probably due to how dopamine neurons receive signals and the way they are organized in the brain. Dopamine neurons are found in the midbrain region of the ventral tegmental area (VTA) and substantia nigra pars compacta projecting to striatal limbic and cortical regions. Dopamine neurons receive information from; hypothalamus and brain stem regions involved in autonomic responses, hippocampus involved in memory, amygdala involved in emotional reactivity, thalamus involved in arousal and prefrontal cortex and cingulate involved in emotional reactivity via neuropeptides and neurotransmitters. Neurochemistry and neuroanatomical reward circuitry involved in addiction to alcohol and drugs translate to an addiction model of overeating and obesity. Certain studies show that hunger can influence memory for food-related stimuli where the orbitofrontal cortex is specifically involved in food-related stimuli in hunger state (Morris and Dolan, 2001). In rodent studies, dopamine has been shown to play a role in feeding by determining a meal size to meal duration, and obesity (Clifton et al., 1991; Schwartz, 2000). Dopamine in the nucleus accumbens has been associated with reinforcement aspects of food and while in the hypothalamus, dopamine plays a role in initiation and duration of feeding (Wang et al., 2004b). Leptin and insulin also help to regulate dopamine production (Leinninger et al., 2009). Dopamine regulates food consumption involving the mesolimbic pathway and the hypothalamus (Volkow et al., 2011). Since dopamine levels in addiction change in these brain regions, it is conceivable that a similar mechanism of reinforcement of food may also be involved in food addiction (Wang et al., 2004b).
Food reward, addiction, and obesity
Food is a natural reward and has both homeostatic and hedonic characteristics (Rada et al., 2010; Volkow et al., 2011). Depending on the specific type of highly palatable food, it has the potential to engage similar brain reward pathways as drugs of abuse (Weatherford et al., 1990; Pitchers et al., 2010; Olsen, 2011). It may also arise from casual eating to compulsive eating that eventually leads to addiction (Davis, 2013). This may be from food-related brain changes that is associated with psychological changes like that seen in drug addiction (Robinson and Berridge, 2003). Both rewarding and hedonic effects of food result in positive emotional reactions that play a major role in overeating and obesity (Fulton, 2010; Avena et al., 2013; Bongers et al., 2013; Sinha and Jastreboff, 2013; Yau and Potenza, 2013). Theoretical models support food addiction because highly palatable food activates reward pathways that lead to human and animal obesity (Finlayson et al., 2007; Berner et al., 2008; Heyne et al., 2009; Davis et al., 2011; Sampey et al., 2011; Akubuiro et al., 2013; Davis, 2013).
The American Psychological Association in the DSM-5 manual included behavioral addiction and addictions to natural rewards as a new category of “addiction and related behavior” (Volkow and O'brien, 2007). Human and rodent studies suggest that dysregulated brain reward pathways may contribute to increased intake of palatable food leading to obesity (see review by Berthoud et al., 2011). Despite the divergence in eating behavior, there is an overall increase in tasty, energy- rich foods that is independent of stress-induced hyperphagia or hypophagia (Gibson, 2006; Dallman, 2010). One hallmark of food addiction is the food craving where intense desired food consumption only compensates the craving, whereas in hunger various types of food alleviates the hunger (Martin et al., 2011). Advantages of functional magnetic resonance imaging (fMRI) and positron emission topography (PET) paradigms have been used to provide insights of neural correlates in food addiction and obesity (Wang et al., 2004a; Teegarden and Bale, 2007; Volkow et al., 2012). Interestingly, following various types of food presentation to normal healthy patients, activated brain regions of anterior cingulate cortex, orbitofrontal cortex, and insula are observed (Wang et al., 2004a; Teegarden and Bale, 2007). In contrast to obese overeating patients, neurobiological changes in the reward pathways are similar to those observed in drug addicts (Volkow et al., 2012). However, available data in humans on food addiction suggests that there is heterogeneity in the clinical definitions of food addiction, obesity, and binge eating disorder. Nonetheless through neurobiological data obtained from both human and animal studies, food cravings, overeating, and tolerance support an addiction-like model, see reviews (Albayrak et al., 2012; Volkow et al., 2012; Davis, 2013; Hone-Blanchet and Fecteau, 2014).
Society and food addiction
Globally about 1 billion adults are overweight of which 475 million are obese (Organization, 2013). Obesity is a complex multifactorial disease. In the United States, increased incidence of adult obesity is on the rise. In the Westernized society, the major cause of obesity is due to reduced physical activity leading to sedentary life style and surplus of food, sodas, variety of fast food, and hyperpalatable foods, all that activate dopamine rewarding centers leading to over consumption of food (Fortuna, 2012; Granados et al., 2012; Ziauddeen et al., 2012). Hyper-palatable foods and their increased availability promote addictive and compulsive eating leading to weight gain. Addictive properties of certain types of food and addiction-like behaviors are observed in both humans and animal models. Animal studies have shown an overview of addiction-like eating behaviors when presented with foods high in sugar and fat (Avena et al., 2008, 2012). In animals, several studies of sugar-binging models support an addiction-like phenotype of tolerance, cross sensitization, withdrawal, and neurochemical changes, but does not induce obesity (Avena, 2007; Avena et al., 2008, 2009). On the other hand, several imaging studies from obese population shows that greater BMI and overeating are associated with neurobiological pathways similar to those observed in drug addicts (Stice and Dagher, 2010; Stice et al., 2010; Volkow et al., 2012, 2013). In humans, feeding behaviors are more complex but pattern of food addiction appears to parallel substance dependence (Gearhardt et al., 2011; Dileone et al., 2012). Some argue that food addiction should be included in the DSM manual (Volkow and O'brien, 2007; Taylor et al., 2010) even though food addiction is not a categorized diagnosis within DSM-5. However, recently Yale Food Addiction Scale (YFAS) has been used as a tool for diagnosis of food addiction in patients with eating disorders (Gearhardt et al., 2009; Clark and Saules, 2013). In one study, using body mass index, body fat percentage by dual-energy X-ray absorptiometry, macronutrient intake, and the YFAS scale has been used as a diagnostic tool to assess food addiction in general Newfoundland population (Pedram et al., 2013). They found that the prevalence of food addiction was significantly associated with obesity in general population. Thus, suggesting that food addiction contributes to severity of obesity in the general population and that food addiction could be a separate etiology of obesity.
In summary, findings of central mediated food intake suggest a complex two-way link between food intake and mood, emotion, reward, food, food choice, and neurotransmitters (Figure 1). Food addiction remains as an incomplete described phenomenon due to limited data. Overabundance of food seems to aid in food addiction specifically foods rich in fat and sugar. Although FMRI and PET imaging have been useful in providing some insights into neural correlates in food addiction and obesity, but specific food addiction phenotype in the development of obesity needs to be differentiated. Furthermore, molecular pathways or signatures that link food intake in emotion, mood, food, reward, and obesity are areas that need further investigation. These types of studies in the future will provide further insight into genetic, psychological, neuropsychiatric, and environmental risk factors associated with overeating, food addiction, and obesity.
Peripheral system in regulation of mood, food, and obesity
The gut-brain axis mediates the communication between brain and gut when it comes to appetite, satiety, and energy homeostasis (Cummings and Overduin, 2007; Ahima and Antwi, 2008; Blevins and Baskin, 2010; Gibson et al., 2010; Suzuki et al., 2010, 2012). Furthermore, peripheral hormones have also been reported to regulate mood, food intake, and obesity (Tschop et al., 2000; Nakazato et al., 2001; Olszewski et al., 2008; Blevins and Baskin, 2010; Suzuki et al., 2010; Andrews, 2011b; Dickson et al., 2011; Egecioglu et al., 2011; Skibicka and Dickson, 2011; Overduin et al., 2012; Perello and Zigman, 2012; Karra et al., 2013). Gastrointestinal signals such as cholecystokinin (CCK), bombesin, glucagon eneterostatin, insulin, resistin, somatedin, cyclohistiyl-proline, leptin, amylin, and apolipoprotein A-IV are all known to reduce food intake. The exception is ghrelin, which increases food intake. Several peripheral factors that engage the CNS in a bi-directional manner and influence mood and food intake are summarized in Table 1 and discussed below.
A gut orexigenic hormone ghrelin is synthesized in the stomach and acts centrally to mediate increased food intake via central pathways (Kojima et al., 1999, 2004; Tschop et al., 2000; Nakazato et al., 2001; Andrews, 2011a; Diz-Chaves, 2011). The hypothalamus in the brain directly senses peripheral ghrelin and modifies the energy status (Schaeffer et al., 2013). Studies support that ghrelin reaches the brain via the vagus afferents to the nucleus solitary tract (NST), which further projects to the arcuate nucleus of the hypothalamus (Asakawa et al., 2001; Date et al., 2002; Williams and Mobarhan, 2003). Ghrelin activates downstream signaling via the hormone secretagogue receptor (GSH-R1a) where it is ubiquitously expressed in multiple brain regions and in peripheral tissues. Due to multiple sites of GSH-R1a expression, it is not surprising that ghrelin performs many other biological activities of growth hormone secretion, glucose and lipid metabolism, and gastrointestinal motility. However, other properties of GHS-R1a allowing dimerization with multiple G-protein coupled receptors suggest the likelihood of cross talk between many other neuropeptide systems of serotonin and dopamine (Schellekens et al., 2013a,b). Thus, ghrelin has the potential to engage multiple neuropeptide systems in mood, food, and obesity.
The ghrelinergic system also mediates the non-homeostatic hedonic rewarding and motivational aspects of food intake via mesolimbic dopaminergic circuitry (Dickson et al., 2011; Egecioglu et al., 2011; Skibicka et al., 2011; Perello and Zigman, 2012). Studies support ghrelin's involvement in stress mediated food reward behavior (Perello et al., 2010; Kumar et al., 2013; Chuang et al., 2011; Diz-Chaves, 2011). Numerous studies provide a link between ghrelin and affective disorders, such as depression and anxiety (Schanze et al., 2008; Barim et al., 2009; Kluge et al., 2009). Ghrelin also alleviates depression (Kluge et al., 2011). All together these studies suggest that the ghrelinergic system is an attractive system to target stress associated metabolic and mood associated eating disorders in obesity.
Serotonin has numerous functions besides regulating mood that includes regulation of sleep, appetite, and impulse control (Steiger, 2004; Daubert and Condron, 2010; Nordquist and Oreland, 2010; Mosienko et al., 2012). Serotonin levels from the gut and alimentary canal constitutes about 80–90% of the human body's total serotonin and not in the brain. This is surprising, as serotonin dictates most of our mood and happiness (Wurtman and Wurtman, 1989; Benton and Donohoe, 1999). Central serotonin pathways participate in the regulation of mood and modulate meal patterns in terms of quality and quantity. Neurotransmitter release of serotonin from serotonergic neurons in the brain is governed by food intake (Shabbir et al., 2013). The essential amino acid tryptophan that comes from food is the precursor for serotonin synthesis (Prasad, 1998). Ingestion of carbohydrates increases the plasma ratio of tryptophan to other large neutral amino acids leading to increased serotonin synthesis in the brain and alleviating depression. Such is the case for carbohydrate craving during depression that often leads to obesity and vice versa (Pepino et al., 2009; Shabbir et al., 2013). This is observed during stress, winter depression, or in people trying to give up smoking. Nicotine increases brain serotonin secretion and its withdrawal leads to depression (Wallin and Rissanen, 1994; Wurtman and Wurtman, 1996). Brain serotonin plays a role in the pathophysiology of depression, as treatments with serotonin potentiating drugs alleviates depression in seasonal affective disorder (Wurtman, 1993). Based on these findings it has been suggested that the excessive carbohydrate intake by patients with premenstrual syndrome (PMS) and seasonal affective disorder (SAD) relieves the depressive symptoms via an increased central serotonergic activity (Cizza et al., 2005; Miller, 2005