nutritional disorders
Obesity
Etiology of Obesity
Causes of obesity are multifactorial and include genetic predisposition and behavioral, metabolic, and hormonal influences. Ultimately, obesity results from a long-standing imbalance between energy intake and energy expenditure, including energy utilization for basic metabolic processes and energy expenditure from physical activity. However, many other factors appear to increase a person's predisposition to obesity, including endocrine disruptors (eg, bisphenol A [BPA]), gut microbiome, sleep/wake cycles, and environmental factors. Heritability of BMI is high across different age groups, ranging from 40 to 60% ( Etiology references , Preabsorptive and postabsorptive signals from the gastrointestinal tract and changes in plasma nutrient levels provide short- and long-term feedback to regulate food intake: Gastrointestinal hormones (eg,glucagon-like peptide 1 [GLP-1], cholecystokinin [CCK], peptide YY [PYY]) reduce food intake. Ghrelin, secreted primarily by the stomach, increases food intake. Leptin, secreted from adipose tissue, informs the brain how much fat is stored. Leptin suppresses appetite in normal-weight people, but high leptin levels correlate with increased body fat. Leptin levels can decrease when weight is lost and then send a hunger signal to the brain. The hypothalamus integrates various signals involved in the regulation of energy balance and then activates pathways that increase or decrease food intake: Neuropeptide Y (NPY), agouti-related peptide (ARP), alpha-melanocyte–stimulating hormone (alpha-MSH),cocaine- andamphetamine-related transcript (CART), orexin, and melanin-concentrating hormone (MCH) increase food intake. Corticotropic hormone (CRH) and urocortin decrease it. The limbic system (amygdala, hippocampus, and prefrontal cortex) mediates the hedonistic pathway for food intake, including cravings, habit, and reward. The desire to eat can override homeostatic pathways because emotion and stress have been shown to affect regulatory peptides such as ghrelin. These effects are mediated bydopamine. Genetic factors also regulate energy expenditure, including basal metabolic rate, diet-induced thermogenesis, and nonvoluntary activity–associated thermogenesis. Genetic factors may have a greater effect on the distribution of body fat, particularly abdominal fat (which increases the risk of Metabolic Syndrome ), than on the amount of body fat. Weight is gained when caloric intake exceeds energy needs. Important determinants of energy intake include Portion sizes The energy density of the food Systemic drivers of lifestyle and behavioral factors are rooted in community culture and economic systems. Communities which do not have access to fresh fruits and vegetables and which do not consume water as the main fluid consumed tend to have higher rates of obesity. High-calorie, energy-dense foods (eg, processed foods), diets high in refined carbohydrates, and consumption of soft drinks, fruit juices, and alcohol promote weight gain. Access to safe recreational spaces (eg, pedestrian and biking infrastructure, parks) and availability of public transportation can encourage physical activity and help protect against obesity. Prenatal maternal obesity, prenatal Social and Illicit Drugs During Pregnancy , excessive weight gain during pregnancy (see table The composition of the gut microbiome also appears to be an important factor; early use of antibiotics and other factors that alter the composition of the gut microbiome may promote weight gain and obesity later in life ( Etiology references ). Early exposure to obesogens, a type of endocrine-disrupting chemical (eg, cigarette smoke, bisphenol A, air pollution, flame retardants, phthalates, polychlorinated biphenyls) can alter metabolic set points through epigenetics or nuclear activation, increasing the propensity of developing obesity ( Regulatory factors ). Adverse childhood events or abuse in early childhood increase risk of several disorders, including obesity. The Centers for Disease Control and Prevention's adverse childhood events study demonstrated that childhood history of verbal, physical, or sexual abuse predicted an increase of 8% in risk of a BMI ≥ 30 and 17.3% in risk of a BMI ≥ 40. Certain types of abuse carried the strongest risk. For example, frequent verbal abuse had the largest increase in risk (88%) of a BMI > 40. Being often hit and injured increased the risk of BMI > 30 by 71% ( Etiology references ). Cited mechanisms for the association between abuse and obesity include neurobiologic and epigenetic phenomena ( Insufficient sleep (usually considered < 6 to 8 hours/night) can result in weight gain by changing the levels of satiety hormones that promote hunger. In the Wisconsin Sleep Cohort Study involving 1024 healthy adults, a decrease in sleep was proportional to an increase in BMI. In adults, BMI increased by 3.6% when average sleep time decreased from 8 hours to 5 hours ( Etiology references ) Smoking cessation is associated with weight gain and can deter patients from quitting smoking. Medications, including corticosteroids,lithium, traditional antidepressants (tricyclics, tetracyclics, monoamine oxidase inhibitors [MAOIs]), benzodiazepines, antiseizure medications, thiazolidinediones, beta-blockers, and antipsychotic medications, can cause weight gain. Uncommonly, weight gain is caused by one of the following disorders: Alternations in brain structure and function caused by a tumor (especially a craniopharyngioma) or an infection (particularly those affecting the hypothalamus), which can stimulate consumption of excess calories Hyperinsulinism due to Overview of Pancreatic Endocrine Tumors None Hypercortisolism due to Cushing Syndrome , which causes predominantly abdominal obesity Hypothyroidism (rarely a cause of substantial weight gain) Male Hypogonadism None At least 2 pathologic eating patterns may be associated with obesity: Binge Eating Disorder None Night-eating syndromeconsists of morning anorexia, evening hyperphagia, and insomnia, with eating in the middle of the night. At least 25 to 50% of daily intake occurs after the evening meal. About 10% of people seeking treatment for severe obesity may have this disorder. Rarely, a similar disorder is induced by use of a hypnotic such aszolpidem. Similar but less extreme patterns probably contribute to excess weight gain in more people. 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