Obesity in adults: Etiologies and risk factors

INTRODUCTION — Obesity is a chronic, often progressive metabolic disease, associated with an increase in mortality and morbidity, that is increasing in prevalence in adults. This topic will review factors that are associated with and promote the development of obesity. The etiology of obesity in children and adolescents is reviewed separately. The specific genetic causes of obesity, as well as the evaluation, prevalence, and treatment of obesity in adults, are also discussed separately:

●(See "Definition, epidemiology, and etiology of obesity in children and adolescents".)

●(See "Obesity: Genetic contribution and pathophysiology".)

●(See "Overweight and obesity in adults: Health consequences".)

●(See "Obesity in adults: Prevalence, screening, and evaluation".)

●(See "Obesity in adults: Overview of management".)

OBESITY AS A DISEASE — Obesity is the result of long-term positive energy balance where energy intake exceeds energy expenditure [1]. Many health care providers and patients share the belief that obesity is the product of poor lifestyle choices that are under the voluntary control of affected individuals. This can lead to stigmatization of people with obesity and a reluctance to use the full range of available treatments [2]. It is now generally recognized that body weight is a physiologically regulated parameter, and obesity is recognized as a disease of body weight regulation, much as diabetes is a disorder of glucose regulation and hypertension is a disorder of blood pressure regulation [3,4]. There are many factors that may contribute to the development of obesity, including genetics, age, lifestyle factors, medications, and hormonal issues.

GENETICS OF OBESITY — Studies suggest that the genetic contribution to adult body mass index (BMI) is 40 to 70 percent in most individuals [5,6]. If a young person has one biological parent with obesity, their risk of obesity is increased three- to fourfold compared with those who do not [7]. Having two biological parents with obesity is associated with a greater than 10-fold increased risk of obesity. However, despite the identification of hundreds of genetic loci associated with obesity in genome-wide association studies, genetic testing of patients with “common” (ie, not syndromic) obesity is not clinically useful [8].

Rare forms of obesity result from certain genetic abnormalities, including Prader-Willi syndrome, Bardet-Biedl syndrome, and the monogenic obesities: melanocortin 4 receptor deficiency (the most common), leptin and leptin receptor deficiencies, and proopiomelanocortin (POMC) deficiency [9]. Monogenic and syndromic obesity typically present as early-onset (<5 years of age) severe obesity, and they are associated with other signs and symptoms.

A detailed discussion of the genetic contribution to obesity, including syndromic and monogenic forms of obesity, is found elsewhere. (See "Obesity: Genetic contribution and pathophysiology".)

DEMOGRAPHIC FACTORS — In the United States, there are regional variations in the prevalence of obesity, with rates ranging from 13 to 50 percent in different counties. Socioeconomic and environmental factors account for 33 and 15.5 percent of the variance, respectively [10]. Obesity prevalence is lowest among those with the highest income and the most education [11]; these relationships are independent of race and ethnicity. In addition, the prevalence of obesity varies among different United States populations. As an example, in 2017 to 2018, the lowest prevalence of obesity was among non-Hispanic Asian adults (17 percent) compared with non-Hispanic White adults (42 percent), Hispanic adults (44 percent), and non-Hispanic Black adults (50 percent) (figure 1) [12]. This is likely related to the social determinants of health, such as elements of the built environment that promote physical activity (eg, availability of sidewalks and playgrounds) [13] and the food environment, that promote or inhibit the consumption of a healthy diet [14].

Further discussion of the epidemiology of obesity is found elsewhere. (See "Obesity in adults: Prevalence, screening, and evaluation", section on 'Prevalence'.)

AGE AND WEIGHT — Prenatal and childhood factors, as well as weight trajectories observed with aging, can predispose to the development of adult obesity.

Fetal and childhood factors — Early life events can predispose to obesity in adult life. Both maternal obesity and undernutrition are associated with adult obesity in offspring [15]. Undernutrition in the first trimester followed by excessive nutrient availability in the postpartum period and infancy are particularly associated with obesity in adulthood [16]. Elevated maternal body mass index (BMI) has been associated with increased fat mass in infants and an increased risk of obesity and metabolic disease in adult offspring [17]. Excessive gestational weight gain, gestational diabetes, and maternal type 2 diabetes can all predispose to adult obesity in offspring, demonstrating that both maternal BMI and glycemia play a role in determining adiposity in offspring [18].

Maternal obesity is believed to alter the development of brain regions involved in body weight regulation and peripheral tissues, including adipose tissue and liver, through epigenetic changes that alter gene expression in these tissues [19]. These epigenetic changes, potentially the result of increased delivery of nutrients from the mother to the developing fetus, promote increased appetite and fat storage in offspring. Gestational, infancy, and childhood contributions to adult obesity are reviewed in detail elsewhere. (See "Definition, epidemiology, and etiology of obesity in children and adolescents", section on 'Persistence into adulthood' and "Definition, epidemiology, and etiology of obesity in children and adolescents", section on 'Metabolic programming'.)

Weight gain in adulthood — Adults tend to gradually gain weight between the ages of 20 to 65. As a result, the long-term risk of becoming overweight (BMI ≥25 kg/m²) or obese (BMI ≥30 kg/m²) over the course of one's life are high. In a prospective cohort study including 4117 normal-weight United States adults ages 30 to 59 years at baseline [20]:

●Within four years, 14 to 19 percent of females and 26 to 30 percent of males became overweight; 5 to 9 percent of all subjects developed obesity.

●Within 30 years, more than 50 percent of participants became overweight; approximately 30 percent of females and 25 percent of males developed obesity.

Between the ages of 20 to 65, a typical adult will consume more than 17,000 pounds of food while only gaining about one to two pounds per year [21]. It is estimated that the energy imbalance responsible for the increased prevalence of obesity over the last 30 years is just 100 kcal/day [22], demonstrating that even a small daily positive energy balance would lead to clinically significant weight gain if sustained for many years. This degree of energy imbalance is difficult for an individual to perceive; clinicians routinely encounter patients with weight gain despite reporting eating a calorie-restricted diet and exercising regularly. Such individuals have been studied under controlled conditions, and results reveal that they underreport energy intake [23]. In fact, underreporting of energy intake and overreporting of physical activity is found consistently in studies [24]. Rather than challenging their patients’ self-reported caloric intake and physical activity, clinicians can reflect on how difficult weight loss is in the face of strong biological systems that defend weight and promote weight gain, and also educate and encourage patients about the value of self-monitoring to gain insight into opportunities for lifestyle change.

Weight tends to rise until roughly the age of 65. After that, weight falls at a rate of 0.65 kg/year on average, although this decline is quite variable between individuals [25]. This occurs in part due to a decrease in muscle mass (sarcopenia), which begins even in the 40s. Fat mass, by contrast, continues to increase into old age, resulting in a decreased association of BMI with fat mass [26]. Energy expenditure declines with aging; -165 kcal/day/decade of life in males and -103 kcal/day/decade of life in females [27]. This is due to a decline in resting energy expenditure (REE) as well as decreased energy expended in physical activity. Older individuals report less hunger during dietary restriction and sense hypoglycemia less well than younger people. Taste and smell can become impaired with aging and can also contribute to decreased food consumption (ie, energy intake).

Further details of energy balance and weight homeostasis are reviewed elsewhere. (See "Obesity: Genetic contribution and pathophysiology", section on 'Physiological processes affecting energy balance'.)

Pregnancy and weight — Weight gain is a physiological consequence of a normal pregnancy, but for many individuals, weight gained during pregnancy is not completely lost following delivery, leading to progressive weight gain over multiple pregnancies and, for some, the development of obesity [28]. Individuals experience modest increases in weight and central adiposity following a first pregnancy. These changes can persist and may vary according to race and ethnic background [29,30]. The National Academy of Medicine suggested that pregnancy weight gain goals be tailored to the individual’s pre-pregnancy weight category (table 1) [31], and the subsequent LifeCycle Project has given further recommendations for individuals in different categories of obesity (table 2). In the United States, 47 percent of females gain more than the recommended amount during pregnancy (figure 2) and individuals who are overweight or obese at baseline are more likely to gain excessive weight gain [32].

Weight gain and management in pregnancy is reviewed in detail elsewhere. (See "Gestational weight gain", section on 'Recommendations for gestational weight gain'.)

Menopause and weight — In females, weight gain and increased central fat distribution often occur in the early postmenopausal years [33]. The magnitude of the increase depends upon the method of measurement [30]. The increase in fat mass with preferential accumulation of visceral fat is felt to be due to reductions in energy expenditure in menopause [34]. The increased levels of follicle-stimulating hormone (FSH) that occur with menopause may be involved in this weight gain independent of the fall in estrogen [35]. (See "Clinical manifestations and diagnosis of menopause", section on 'Long-term consequences of estrogen deficiency'.)

In the Study of Women's Health Across the Nation (SWAN) including almost 550 females aged 42 to 52 at baseline, weight, waist circumference, and fat mass (measured with bioelectrical impedance) were followed for six years [36]. Over the study period, there was an average 2.9 kg weight gain, 3.4 kg increase in fat mass, and a 5.7 cm increase in waist circumference. Among study subjects, the rate of waist circumference increase slowed one year after the final menstrual period, whereas fat mass continued to increase without change.

However, estrogen therapy does not prevent weight gain in postmenopausal females, although it may minimize fat redistribution [37,38]. In a three-year trial including over 800 participants from the Women's Health Initiative (WHI), those who received estrogen and progesterone therapy lost less lean muscle mass (-0.04 versus -0.44 kg) and had less change in fat distribution compared with those receiving placebo [37]. However, the effects were small and the clinical benefits unclear. In a metanalysis including 28 randomized trials and over 28,000 participants, the use of post-menopausal estrogen alone or combination estrogen and progesterone was not associated with a change in body weight [39]. (See "Menopausal hormone therapy: Benefits and risks", section on 'Weight'.)

LIFESTYLE CONTRIBUTORS — Weight gain occurs when energy intake exceeds energy expenditure, and lifestyle factors including diet and physical activity impact this balance.

Dietary factors — Globally, the food environment has changed dramatically over the last 70 years, providing people access to highly palatable, energy-dense food. It is difficult, however, to get accurate information on energy intake since self-reported dietary data are notoriously unreliable. According to the US Department of Agriculture (USDA) data on the food energy supply, average food intake in the United States has increased over the past several decades. In the 1970s, intake was 2398 kcal/day/person and increased to 2895 kcal/day/person in the 2000s. This increase in energy intake is sufficient to account for the increase in the prevalence of obesity observed over this time [40].

These USDA data also suggest that Americans are eating more fat, sugar, proteins, and grains and less fruit, vegetables, and dairy than recommended [40,41]. Although dietary macronutrient composition has been evaluated with regards to risk of weight gain, there is no conclusive evidence that a diet high in either fat or carbohydrates is consistently associated with weight gain [1].

The quality of the diet and its components are being evaluated for their role in weight gain. In a longitudinal study including over 120,000 adults, increase in the intake of specific foods have been associated with either weight gain (eg, potato chips, French fries, processed meats, red meat, sweets and desserts) or protection against weight gain (yogurt, fruit, whole grains, nuts, vegetables) (figure 3) [42]. In addition, observational studies have found an association between the consumption of ultraprocessed foods (eg, foods that have undergone multiple physical, biological, and/or chemical processes that are associated with industrial food production and typically contain food additives) with the development of obesity [43]. In a randomized controlled trial including 20 adults comparing two weeks of ad-libitum consumption of an ultraprocessed diet with an unprocessed diet, consumption of an ultraprocessed diet increased energy intake (+508 kcal/day) and weight (+0.9 kg), while consumption of an unprocessed diet decreased weight (-0.9 kg) [44].

The role of diet and dietary changes in managing obesity are reviewed elsewhere. (See "Obesity in adults: Dietary therapy", section on 'Our approach'.)

Physical activity and inactivity — The most variable component of energy expenditure is energy expended in physical activity. Reductions in habitual levels of physical activity along with increased time spent in sedentary behaviors have been associated with an increased risk of obesity [45]. According to a Surgeon General's Report of Physical Activity, the percent of adult Americans participating in physical activity decreases steadily with age, and reduced energy expenditure in adults and children is predictive of weight gain [46].

●Comparing Pima populations living in Mexico and the United States, those living a traditional agrarian lifestyle in remote northern Mexico have low levels of obesity and type 2 diabetes [47]. By contrast, more than 80 percent of the adult Pima population living in Arizona have obesity. In the study, energy expenditure was 3289 kcal/day in the Mexican Pima population compared with 2671 kcal/day in the United States Pima population.

●Occupational physical activity has fallen in the United States over the last 50 years, during which the prevalence of obesity has grown [48]. In 1960, approximately half of the United States workforce was moderately active on the job, but as of 2010, >70 percent of workers were either sedentary or reported a light physical workload. This represents an average decline in work-related energy expenditure of 140 kcal/day in males and 120 kcal/day in females, further contributing to an increasing prevalence of obesity.

●In data from the 2003 to 2006 National Health and Nutrition Examination Survey (NHANES), obesity was more strongly related to moderately vigorous physical activity than either TV time or total sedentary time for adults in the United States [49]. Small differences in daily levels of moderately vigorous physical activity (5 to 10 minutes) were associated with relatively large differences in obesity risk.

●Time spent sitting and in sedentary behaviors is associated with adverse metabolic health outcomes such as type 2 diabetes, but the relationship between sedentary behaviors and obesity has been harder to demonstrate [50]. Of all sedentary behaviors, prolonged television watching appears to be the most closely associated with the risk of obesity and diabetes [51]. In the Nurses' Health Study, after adjusting for age, exercise level, and dietary factors, every two-hour increment spent watching television was associated with an increase in the risk of obesity and diabetes (23 percent, 95% CI 17 -30; and 14 percent, 95% CI 5-23, respectively) [52]. Less risk was associated with other sedentary behavior such as sitting at work. The effects of television watching on obesity may be mediated, in part, by increases in energy intake (eg, associated eating behaviors) rather than a decrease in physical activity alone [53,54].

●Obesity is more prevalent in adults with physical, sensory, or mental health disabilities; those with impaired lower-extremity mobility are at highest risk [55].

The role of physical activity in the management of obesity is reviewed separately. (See "Obesity in adults: Role of physical activity and exercise".)

Sleep patterns — Epidemiological studies show strong and consistent associations between shortened nocturnal sleep time, late bedtime, and nightshift work with the development of obesity, type 2 diabetes mellitus, and related metabolic disorders [56,57]. Although the average adult sleep duration has not changed over the past half-century [58], the number of people performing nightshift work has increased, with many employees working during what is typically considered sleep time [56].

Individuals who have shortened sleep duration or a nightshift schedule spend more time in sedentary activities and less time in moderate and vigorous physical activity compared with people on a normal sleep schedule. In experimental studies, these changes lead to a reduction in total daily energy expenditure [59,60]. Studies have also shown that with sleep restriction, brain regions associated with food reward are activated and measured food intake, particularly high-fat foods, increases [61]. With sleep restriction, levels of satiety hormones are lower and levels of ghrelin higher. By contrast, extending sleep duration may lead to reduced energy intake [62].

Smoking cessation — Despite clear health benefits, smoking cessation is associated with an average weight gain of 2.6 kg [63]. The degree of weight gain is highly variable, with 10 percent of quitters gaining 10 kg at one year. This weight gain may in part be due to a loss of nicotine’s activating effects on proopiomelanocortin (POMC) neurons in the hypothalamus, which decrease food intake [64].

MEDICATIONS ASSOCIATED WITH WEIGHT GAIN — A variety of medications prescribed for common health problems have been associated with weight gain (table 3) [65]. Within each category, there are alternatives that are either weight-neutral or may promote weight loss.

●Antipsychotic agents – Antipsychotic drugs have a variable effect on body weight, although many agents are associated with weight gain (table 3) [66]. Among the conventional (first-generation) antipsychotics, the estimated average weight gain after 10 weeks of therapy was highest for thioridazine (3.2 kg). Molindone did not cause weight gain.

Among the atypical (second-generation) antipsychotics, clozapine and olanzapine are associated with the greatest weight gain (4.4 and 4.2 kg, respectively), followed by risperidone (2.10 kg) [66]. (See "First-generation antipsychotic medications: Pharmacology, administration, and comparative side effects" and "Second-generation antipsychotic medications: Pharmacology, administration, and side effects" and "Schizophrenia in adults: Maintenance therapy and side effect management", section on 'Side effect management'.)

Lithium, a mood stabilizer used for the treatment of bipolar disorder, is associated with weight gain. (See "Bipolar disorder in adults: Choosing maintenance treatment", section on 'Lithium'.)

●Antidepressants – There are many antidepressants which are associated with weight gain, including the tricyclics, monoamine oxidase inhibitors (MAOIs), and some of the selective serotonin reuptake inhibitors (SSRIs) (table 4).

Tricyclic antidepressants, in particular amitriptyline, clomipramine, doxepin, and imipramine, are associated with significant weight gain. (See "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects", section on 'Side effects'.)

The effects of the SSRIs on body weight are less well characterized; the impact of these agents on weight is variable and may depend on the particular agent and the duration of use. Short-term use of fluoxetine and sertraline has been associated with weight loss [67,68]. By contrast, long-term use of some, but not all, SSRIs may be associated with weight gain. As an example, in a randomized trial including 284 patients with depression receiving fluoxetine, sertraline, or paroxetine for 26 to 32 weeks, those receiving only the paroxetine group had a significant weight change compared with baseline (3.6 percent increase) [69]. (See "Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects", section on 'Weight change'.)

●Antiseizure medications – Several antiseizure medications, particularly valproate, carbamazepine, and gabapentin, used to treat seizures, neuropathic pain, and psychiatric conditions such as bipolar disorder, are associated with weight gain (table 5 and table 3). (See "Overview of the management of epilepsy in adults", section on 'Choosing an antiseizure medication' and "Bipolar major depression in adults: Choosing treatment", section on 'Choosing pharmacotherapy' and "Rapid cycling bipolar disorder in adults: Treatment of mania and hypomania" and "Rapid cycling bipolar disorder in adults: Treatment of major depression".)

●Hypoglycemic medications – Several medication classes used to treat diabetes are associated with modest weight gain, particularly insulin and the sulfonylureas (table 3) [66].

Compared with conventional insulin therapy, intensive insulin therapy results in greater weight gain. As an example, in the Diabetes Control and Complications Trial, the mean weight gain was greater in the intensive-treatment group compared with the usual care group (5.1 kg versus 2.4 kg) [70]. (See "Glycemic control and vascular complications in type 2 diabetes mellitus".)

The thiazolidinediones, such as pioglitazone and rosiglitazone, are also associated with weight gain, although this may be due to fluid retention and/or fat redistribution.

Metformin does not cause weight gain and may be associated with weight loss. In the Diabetes Prevention Program, metformin was associated with modest, prolonged weight loss (approximately 2 kg) in patients with impaired glucose tolerance [71]. Other diabetes medications are either weight-neutral (ie, dipeptidyl peptidase-4 [DPP-4] inhibitors) or associated with more significant weight loss (ie, glucagon-like peptide 1 [GLP-1] receptor agonists, sodium-glucose co-transporter 2 [SGLT2] inhibitors, alpha-glucosidase inhibitors). The weight effects of diabetes medications are reviewed in detail elsewhere. (See "Thiazolidinediones in the treatment of type 2 diabetes mellitus" and "Metformin in the treatment of adults with type 2 diabetes mellitus" and "Insulin action" and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Weight loss' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Weight loss'.)

●Hormonal contraception – Although it is a common belief that oral contraceptives cause weight gain, data suggest that significant weight gain is not a common side effect of combined oral contraceptives at contemporary doses [72]. Progestin-only contraceptives, including depomedroxyprogesterone acetate (DMPA), are considered the hormonal contraceptive preparations most associated with weight gain [73], although a 2019 systematic review found no evidence to support a weight-gain relationship [74]. The variability in weight gain response to progesterone contraceptives may be due to genetic variability. In a study including 276 participants using an etonogestrel implant, those who were homozygous for a particular estrogen receptor variant (ie, ESR1 rs9340799) experienced a 14.1 kg greater weight gain compared with those without the genetic variant [75].

Further details on specific hormonal contraception and weight gain are reviewed elsewhere. (See "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits", section on 'Weight changes' and "Contraception: Progestin-only pills (POPs)", section on 'Side effects' and "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Weight gain'.)

●Other medications – Other drugs associated with weight gain include cyproheptadine (an antihistamine), beta blockers, and glucocorticoids [66]. (See "Major side effects of beta blockers" and "Major adverse effects of systemic glucocorticoids".)

CONDITIONS ASSOCIATED WITH WEIGHT GAIN

Hypothyroidism — Patients with overt clinical hypothyroidism often gain weight, with some of the weight due to increased adiposity. The weight gain, however, is usually modest. Increasing serum thyroid-stimulating hormone (TSH) concentrations within the normal range have also been associated with a modest increase in body weight in adults [76,77], but treatment of subclinical hypothyroidism does not appear to be associated with weight loss. Observational data suggest that obesity may predispose to hypothyroidism, raising questions about causality [78]. Hypothyroidism and weight is reviewed in detail elsewhere. (See "Subclinical hypothyroidism in nonpregnant adults", section on 'Potential consequences' and "Clinical manifestations of hypothyroidism", section on 'Clinical manifestations'.)

Cushing's syndrome — A common feature in patients with Cushing’s syndrome is progressive central adiposity involving the trunk, abdomen, mesentery, and mediastinum. There is usually accumulation of fat tissue in the face and neck, with enlarged dorso- and supraclavicular fat pads. The extremities are usually spared and often exhibit muscular wasting. The excess of glucocorticoids in Cushing’s syndrome (iatrogenic or endogenous) induces 11-beta-hydroxysteroid dehydrogenase type 1 in visceral fat, enhancing its lipogenic capacity [79]. (See "Epidemiology and clinical manifestations of Cushing syndrome".)

Hypothalamic obesity — Hypothalamic obesity is a rare syndrome in humans that can be reproduced in animals by injury to the ventromedial or paraventricular region of the hypothalamus or the amygdala [80]. These regions of the brain are responsible for integrating metabolic information regarding nutrient stores with afferent sensory information about food availability. When the ventromedial hypothalamus is damaged, hyperphagia develops, energy expenditure decreases [81], and obesity follows.

This syndrome can be caused by a tumor (most commonly craniopharyngioma) [82] (see "Craniopharyngioma"), trauma, irradiation, surgery in the posterior fossa, or increased intracranial pressure [83]. In addition to weight gain, additional symptoms may include headache, vomiting, and/or visual changes; amenorrhea, erectile dysfunction, arginine vasopressin deficiency (previously called central diabetes insipidus), hypothyroidism, and/or adrenal insufficiency; seizures, somnolence, coma, and/or disordered temperature regulation [84].

In a report of 42 adults with tumors in the hypothalamic region (treated with surgery and/or radiotherapy), 52 percent of patients had obesity after a median of five years of follow-up (versus 24 percent at baseline) [85]. In a multivariate analysis, no correlation was found between tumor location or size and subsequent weight gain.

Bariatric surgery has been found to produce moderate weight loss in patients with hypothalamic obesity, although the amount of weight lost may be less than what is seen in patients with "typical" obesity [86,87].

Growth hormone deficiency — Growth hormone deficiency in adults is associated with an increase in abdominal and visceral fat. (See "Growth hormone deficiency in adults".)

OTHER POSSIBLE CONTRIBUTORS TO OBESITY

The gut microbiome — The composition of the gut flora, or the gut microbiome, may be a contributor to obesity. Since the observation that germ-free mice weigh less than mice with a normal gut microbiome [88], there have been a large number of studies demonstrating an association between the proportion of Bacteroidetes and Firmicutes bacteria in the gut and the development of obesity. It is less clear, however, that the relationship is causal [89]. The role of the gut microbiome in weight and obesity is reviewed in detail elsewhere. (See "Obesity: Genetic contribution and pathophysiology", section on 'Gut microbiome'.)

Exposure to endocrine-disrupting chemicals — Endocrine-disrupting chemicals are compounds that are used in the production of a wide range of commercial products. They have been found in environmental water samples and the food supply and can accumulate in human tissues. A growing number of studies have linked exposure to these compounds to both childhood and adult obesity [90]. Based on observational studies, bisphenol A and perfluorinated chemicals may be the most strongly associated [91].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Obesity in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Health risks of obesity (The Basics)" and "Patient education: Weight loss treatments (The Basics)")

●Beyond the Basics topics (see "Patient education: Losing weight (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Obesity as a disease – Obesity is the result of long-term positive energy balance where energy intake exceeds energy expenditure. It is now generally recognized that body weight is a physiologically regulated parameter, and obesity is recognized as a disease of body weight regulation. Studies suggest that the genetic contribution to adult body mass index (BMI) is 40 to 70 percent in most individuals. (See 'Obesity as a disease' above and 'Genetics of obesity' above.)

●Age and weight – Prenatal and childhood factors, as well as weight trajectories observed with aging, can predispose to the development of adult obesity. Adults tend to gradually gain weight between the ages of 20 to 65, after which weight declines in most people (figure 4); this weight decline, however, is in part due to loss of muscle mass rather than adiposity. (See 'Fetal and childhood factors' above and 'Weight gain in adulthood' above.)

●Lifestyle contributors to obesity – Lifestyle factors, such as diet, physical activity (and inactivity), sleep patterns, and smoking cessation, are all associated with weight gain. (See 'Lifestyle contributors' above.)

●Medications associated with weight gain – A variety of common medications, including some antipsychotic agents, antidepressants, antiseizure medications, hypoglycemic agents, and hormonal contraceptives, have been associated with weight gain (table 5 and table 3). (See 'Medications associated with weight gain' above.)

●Medical conditions associated with weight gain – Certain medical conditions may be associated with weight gain, including hypothyroidism, Cushing’s syndrome, hypothalamic dysfunction (ie, hypothalamic obesity), and growth hormone deficiency. (See 'Conditions associated with weight gain' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges George Bray, MD, who contributed to an earlier version of this topic review.