Causes

Causative factors

In all individuals, the excess energy utilized to generate fat reserves is minute relative to the total number of calories consumed. This means that very fine perturbations in the energy balance can lead to large fluctuations in weight over time. To illustrate, an obese 40 year old who carries 100 lb of adipose tissue has only consumed about 25 more calories per day than he has burned on average - or the equivalent of an apple every three days. In comparison a very lean 40-year-old who carries only 15 lb of body fat will have exceeded his daily energy expenditure by about four calories a day - the equivalent of an apple every 18 days.

Factors that have been suggested to contribute to the development of obesity include:

• Sedentary lifestyle
• A high glycemic diet (i.e. a diet that consists of meals that give high postprandial blood sugar)
• Weight cycling, caused by repeated attempts to lose weight by dieting
• Underlying illness (e.g. hypothyroidism)
• Genetic disorders (e.g. Prader-Willi syndrome)
• Eating disorders (such as binge eating disorder)
• Stressful mentality
• Insufficient sleep
• Certain medications (e.g. atypical antipsychotics)
• Smoking cessation
• Genetic factors
• Gluttony

As with many medical conditions, the caloric imbalance that results in obesity often develops from a combination of genetic and environmental factors. Polymorphisms in various genes controlling appetite, metabolism, and adipokine release predispose to obesity, but the condition requires availability of sufficient calories, and possibly other factors, to develop fully. Various genetic abnormalities that predispose to obesity have been identified (such as Prader-Willi syndrome and leptin receptor mutations), but known single-locus mutations have been found in only about 5% of obese individuals. While it is thought that a large proportion of the causative genes are still to be identified, much obesity is likely the result of interactions between multiple genes, and non-genetic factors are likely also important.

Some eating disorders are associated with obesity, especially binge eating disorder (BED). As the name indicates, patients with this disorder are prone to overeat, often in binges. A proposed mechanism is that the eating serves to reduce anxiety, and some parallels with substance abuse can be drawn. An important additional factor is that BED patients often lack the ability to recognize hunger and satiety, something that is normally learned in childhood. Learning theory suggests that early childhood conceptions may lead to an association between food and a calm mental state.

Evolutionary aspects

Neurobiological mechanisms

Flier summarizes the many possible pathophysiological mechanisms involved in the development and maintenance of obesity. This field of research had been almost unapproached until leptin was discovered in 1994. Since this discovery, many other hormonal mechanisms have been elucidated that participate in the regulation of appetite and food intake, storage patterns of adipose tissue, development of insulin resistance. Since leptin's discovery, ghrelin, orexin, PYY 3-36, cholecystokinin, adiponectin, and numerous other mediators have been studied. The adipokines are mediators produced by adipose tissue; their action is thought to modify many obesity-related diseases.

Leptin and ghrelin are considered to be complementary in their influence on appetite, with ghrelin produced by the stomach modulating short-term appetitive control (i.e. to eat when the stomach is empty and to stop when the stomach is stretched). Leptin is produced by adipose tissue to signal fat storage reserves in the body, and mediates long-term appetitive controls (i.e. to eat more when fat storages are low and less when fat storages are high). Although administration of leptin may be effective in a small subset of obese individuals who are leptin-deficient, many more obese individuals are thought to be leptin-resistant, and this resistance has been implicated in obesity in some people, is thought to explain in part why administration of leptin has not been shown to be effective in suppressing appetite in most obese subjects.

Neuroscientific approaches hinge on the action of the aforementioned hormones and mediators on the hypothalamus, the part of the brain that is thought to produce hunger signals for higher centers and induce food intake behavior. Lesion studies in the 1940s and 1950s identified two regions of the hypothalamus — the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH) — as the brain's hunger and satiety centers, respectively. Specific lesions to a mouse's LH suppressed its appetite while damaging the VMH caused overeating.

Studies of the distribution of the leptin receptor in the mid-1990s cast doubt upon this dual center theory of hunger and satiety. Leptin's effect on the arcuate nucleus melanocortin system is now considered central to the regulation of feeding and metabolism.

Poverty link

Complications

Apart from the metabolic syndrome, obesity is also correlated (in population studies) with a variety of other complications. For many of these complaints, it has not been clearly established to what extent they are caused directly by obesity itself, or have some other cause (such as limited exercise) that causes obesity as well. Most confidence in a direct cause is given to the mechanical complications in the following list, compiled by the American Medical Association for general physicians:

• Cardiovascular: congestive heart failure, enlarged heart and its associated arrhythmia and dizziness, cor pulmonale, varicose veins, and pulmonary embolism
• Endocrine: polycystic ovarian syndrome (PCOS), menstrual disorders, and infertility
• Gastrointestinal: gastroesophageal reflux disease (GERD), fatty liver disease, cholelithiasis (gallstones), hernia, and colorectal cancer
• Renal and genitourinary: urinary incontinence, glomerulopathy, hypogonadism (male), breast cancer (female), uterine cancer (female), stillbirth
• Integument (skin and appendages): stretch marks, acanthosis nigricans, lymphedema, cellulitis, carbuncles, intertrigo
• Musculoskeletal: hyperuricemia (which predisposes to gout), immobility, osteoarthritis, low back pain
• Neurologic: stroke, meralgia paresthetica, headache, carpal tunnel syndrome, dementia
• Respiratory: dyspnea, obstructive sleep apnea, hypoventilation syndrome, Pickwickian syndrome, asthma
• Psychological: Depression, low self esteem, body image disorder, social stigmatization

While being severely obese has many health ramifications, those who are somewhat overweight face little increased mortality or morbidity. Some studies suggest that the somewhat "overweight" tend to live longer than those at their "ideal" weight ^*. This may in part be attributable to lower mortality rates in diseases where death is either caused or contributed to by significant weight loss due to the greater risk of being underweight experienced by those in the ideal category. Another factor which may confound mortality data is smoking, since obese individuals are less likely to smoke. Osteoporosis is known to occur less in slightly overweight people.

Therapy

A more intractable therapeutic problem appears to be weight loss maintenance. Of dieters who manage to lose 10% or more of their body mass in studies, 80-95% will regain that weight within two to five years. It appears that the homeostatic mechanisms regulating body weight are very robust (see leptin, for example), and vigorously defend against weight loss. Much important research is now being devoted to determining what factors can improve the currently dismal weight loss maintenance rates.

Recent scientific research has cast some doubt over whether or not dieting actually improves health, with some studies indicating that dieting may in fact be more detrimental than remaining overweight

In a clinical practice guideline by the American College of Physicians Fulltext., the following five recommendations are made:

1. People with a BMI of over 30 should be counseled on diet, exercise and other relevant behavioral interventions, and set a realistic goal for weight loss.
2. If these goals are not achieved, pharmacotherapy can be offered. The patient needs to be informed of the possibility of side-effects and the unavailability of long-term safety and efficacy data.
3. Drug therapy may consist of sibutramine, orlistat, phentermine, diethylpropion, fluoxetine, and bupropion. For more severe cases of obesity, stronger drugs such as amphetamine and methamphetamine may be used on a selective basis. Evidence is not sufficient to recommend sertraline, topiramate, or zonisamide.
4. In patients with BMI > 40 who fail to achieve their weight loss goals (with or without medication) and who develop obesity-related complications, referral for bariatric surgery may be indicated. The patient needs to be aware of the potential complications.
5. Those requiring bariatric surgery should be referred to high-volume referral centers, as the evidence suggests that surgeons who frequently perform these procedures have fewer complications.

Much research focuses on new drugs to combat obesity, which is seen as the biggest health problem facing developed countries. Nutritionists and many doctors feel that these research funds would be better devoted to advice on good nutrition, healthy eating, and promoting a more active lifestyle.

Medication most commonly prescribed for diet/exercise-resistant obesity is orlistat (Xenical®, which reduces intestinal fat absorption by inhibiting pancreatic lipase) and sibutramine (Reductil®, Meridia®, an anorectic). In the presence of diabetes mellitus, there is evidence that the anti-diabetic drug metformin (Glucophage®) can assist in weight loss — rather than sulfonylurea derivatives and insulin, which often lead to further weight gain. The thiazolidinediones (rosiglitazone or pioglitazone) can cause slight weight gain, but decrease the "pathologic" form of abdominal fat, and are therefore often used in obese diabetics.

Increasingly, bariatric surgery is being used to combat obesity. The most common weight loss surgery in Europe and Australia is the adjustable gastric band where a silicone ring is placed around the top of the stomach to help restrict the amount of food eaten in a sitting. This surgery has been FDA approved in the United States since 2001 but has been being used in other parts of the world since the early 1990s. It is considered the safest and least invasive of the available weight loss surgeries such as Roux-en-Y gastric bypass surgery (RNY), biliopancreatic diversion, and stomach stapling (also known as "vertical banded gastroplasty", VBG). Unlike those more invasive techniques the band surgery does not cut into or reroute any of the digestive tract and is completely reversible. Removing the implant returns the stomach to its pre-surgical norm. All of these surgeries can be done laparoscopically. The more invasive of the surgeries usually bypass or remove some portion of the patient's intestines which causes malabsorption and dumping. All of these surgeries come with risk to the patient, from the LAP-BAND which has a mortality rate of 1 in 2000 to the RNY Bypass which has a mortality rate of 1 in 200. RNY surgery appears to be popular because the weight tends to come off faster than with the band but studies have shown that at 3-6 years out the amount of weight lost and the amount of loss maintained is nearly identical. Therefore the patient needs to consider the long term ramifications of their choice.

None of these weight loss surgeries should be considered lightly and all risks must be examined and weighed against the risks of remaining obese. Bariatric surgery is not the easy way out, it requires the patient to make lifelong changes to their diet if they are to keep the lost weight off in the long term. Restrictive surgeries such as the adjustable gastric band offer the patient a built-in tool but it should be considered a tool not a magic solution. They can help a person to eat less but they cannot choose what the patient puts in their mouth, thus the need for long term commitments to eat properly.

Cultural and social significance

Etymology

Culture and obesity

In several human cultures, obesity is associated with physical attractiveness, strength, and fertility. Some of the earliest known cultural artifacts, known as Venus figurines, are pocket-sized statuettes representing an obese female figure. Although their cultural significance is unrecorded, their widespread use throughout pre-historic Mediterranean and European cultures suggests a central role for the obese female form in magical rituals, and suggests cultural approval of (and perhaps reverence for) this body form. This is most likely due to their ability to easily bear children and survive famine.

In contrast, in modern Western culture, a more slender body shape is more typically considered desirable. "Thinness" is often considered more important for women than men.

Obesity was occasionally considered a symbol of wealth and social status in cultures prone to food shortages or famine. Well into the early modern period in European cultures, it often served this role. But as food security was realised, it came to serve more as a visible signifier of "lust for life", appetite, and immersion in the realm of the erotic. This was especially the case in the visual arts, such as the paintings of Rubens (1577–1640), whose regular use of the full female figures gives us the description Rubenesque for plumpness. Obesity can also be seen as a symbol within a system of prestige. "The kind of food, the quantity, and the manner in which it is served are among the important criteria of social class. In most tribal societies, even those with a highly stratified social system, everyone - royalty and the commoners - ate the same kind of food, and if there was famine everyone was hungry. With the ever increasing diversity of foods, food has become not only a matter of social status, but also a mark of one's personality and taste." Powdermaker H. "An anthropological approach to the problem of obesity." Food and Culture: A Reader. Ed. Carole Counihan and Penny van Esterik. New York: Routledge, 1997. 206.

Not all contemporary cultures disapprove of obesity, although the Western preference for thinness is increasingly being exported worldwide as part of the process of globalization. Few cultures have escaped the "Westernization" of body shape preference, though cultures which are traditionally more approving (to varying degrees), include some African, Arabic, Indian, and Pacific Island cultures. Especially in the past decades, obesity has come to be seen more as a medical condition. There is also a small but vocal fat acceptance movement that seeks to challenge weight-based discrimination.

Popular culture

Various stereotypes of obese people have found their way into expressions of popular culture. A common stereotype is the obese character who has a warm and dependable personality, but equally common is the obese vicious bully. Gluttony and obesity are commonly depicted together in works of fiction. In cartoons, obesity is often used to comedic effect, with fat cartoon characters having to squeeze through narrow spaces, frequently getting stuck or even exploding.

It can be argued that depiction in popular culture adds to and maintains commonly perceived stereotypes, in turn harming self esteem of obese people. A charge of discrimination on the basis of appearance could be leveled against these depictions.

On the other hand, obesity is often associated with positive characteristics such as good humor (the stereotype of the jolly fat man like Santa Claus), and some people are more sexually attracted to obese people than to slender people (see chubby culture, fat admirer).

Public health and policy