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  • Obesity occurs when there is an imbalance between energy intake and energy expenditure over time, resulting in increased energy storage.


  • The etiology of obesity is usually unknown, but it is likely multifactorial and related to varying contributions from genetic, environmental, and physiologic factors.

  • Genetic factors appear to be the primary determinants of obesity in some individuals, determining both obesity and distribution of fat, whereas environmental factors are more important in others. The total number and identity of contributing genes are still being determined.

  • Environmental factors include reduced physical activity or work, abundant food supply, relatively sedentary lifestyles, increased availability of high-fat foods, and cultural factors and religious beliefs.

  • Medical conditions including Cushing disease, growth hormone deficiency, insulinoma, leptin deficiency, and psychiatric disorders such as depression, binge-eating disorder, and schizophrenia and genetic syndromes such as Prader–Willi syndrome can be associated with weight gain.

  • Medications associated with unintended weight gain include insulin, corticosteroids, some antidepressants, conventional antipsychotics, and several anticonvulsants.

  • Many neurotransmitters and neuropeptides stimulate or depress the brain’s appetite network, impacting total calorie intake.

  • The degree of obesity is determined by the net balance of energy ingested relative to energy expended over time. The single largest determinant of energy expenditure is metabolic rate, which is expressed as resting energy expenditure or basal metabolic rate. Physical activity is the other major factor that affects total energy expenditure and is the most variable component.

  • Major types of adipose tissue are: (1) white adipose tissue, which manufactures, stores, and releases lipid; and (2) brown adipose tissue, which dissipates energy via uncoupled mitochondrial respiration. Adrenergic stimulation activates lipolysis in fat cells and increases energy expenditure in adipose tissue and skeletal muscle.


  • Obesity is associated with serious health risks and increased risk of all-cause mortality. Central obesity reflects high levels of intra-abdominal or visceral fat that is associated with the development of hypertension, dyslipidemia, type 2 diabetes, and cardiovascular disease (sometimes referred to as the “metabolic syndrome”).

  • Body mass index (BMI) and waist circumference (WC) are recognized, acceptable markers of excess body fat that independently predict disease risk (Table 58-1).

  • BMI is calculated as weight (kg) divided by the square of the height (m2).

  • WC, the most practical method of characterizing central adiposity, is the narrowest circumference between the last rib and the top of the iliac crest.

TABLE 58-1Classification of Overweight and Obesity by Body Mass Index, Comorbidity Risk, Waist Circumference, and Associated Disease Risk

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