The control of hunger and satiety in the gastrointestinal (GI) tract involves short-term signals that influence the size and frequency of meals within minutes to hours. In the absence of food intake, the stomach produces ghrelin, an appetite-stimulating hormone called an orexigenic hormone, which induces hunger. As food is consumed, satiety is induced by GI hormones like cholecystokinin and peptide YY, which have an anorexigenic effect. These hormones act on gastric emptying and neural signals to the hypothalamus, terminating eating. Hunger and satiety are regulated within the hypothalamus through the involvement of neuropeptides (such as orexigenic neuropeptide Y [NPY] and anorexigenic α-melanocyte–stimulating hormone [α-MSH]) and neurotransmitters (such as anorexigenic serotonin and dopamine). Long-term and short-term signals interact, with leptin increasing α-MSH secretion and decreasing NPY secretion. Consequently, there are numerous intricate regulatory loops that control the size and frequency of meals based on body fat stores.

The primary metabolic effects of obesity encompass dyslipidemias, glucose intolerance, and insulin resistance predominantly seen in the liver, skeletal muscle, and adipose tissue. These metabolic abnormalities arise from molecular signals originating from the increased mass of adipocytes. However, it is important to note that approximately 30% of obese individuals do not exhibit these metabolic abnormalities.

Abdominal obesity is linked to a cluster of metabolic abnormalities known as the metabolic syndrome, which includes hyperglycemia, insulin resistance, hyperinsulinemia, dyslipidemia (low levels of high-density lipoprotein [HDL] and elevated TAG), and hypertension. The metabolic syndrome is a risk factor for cardiovascular disease (CVD) and type 2 diabetes (T2D). The chronic, low-grade systemic inflammation observed in obesity contributes to the development of insulin resistance and T2D, as well as the metabolic syndrome. Adipocytes in obesity release proinflammatory mediators like IL-6 and TNF-α, while levels of the anti-inflammatory hormone adiponectin, which enhances insulin sensitivity and suppresses inflammation, are reduced.

Obesity is associated with the ectopic deposition of TAG in the liver, leading to an increased risk of nonalcoholic fatty liver disease (NAFLD).

Obesity is correlated with a higher risk of mortality and serves as a risk factor for various chronic conditions, including T2D, dyslipidemias, hypertension, CVD, certain cancers, gallstones, arthritis, gout, pelvic floor disorders (e.g., urinary incontinence), NAFLD, and sleep apnea. The association between obesity and related health issues is stronger in individuals younger than 55 years old, and after the age of 74, there is no longer a connection between increased body mass index (BMI) and mortality. Additionally, obesity has social consequences, such as stigmatization and discrimination. Weight loss in obese individuals leads to reductions in blood pressure, plasma TAG, and blood glucose levels, while increasing HDL levels. 

Weight reduction is crucial in managing obesity.
Short-term signals from the gastrointestinal (GI) tract control hunger and satiety, which affect the size and number of meals over a time course of minutes to hours. In the absence of food intake (between meals), the stomach produces ghrelin, an orexigenic (appetite-stimulating) hormone that drives hunger. As food is consumed, GI hormones, including cholecystokinin and peptide YY, among others, induce satiety (an anorexigenic effect), thereby terminating eating, through actions on gastric emptying and neural signals to the hypothalamus. Within the hypothalamus, neuropeptides (such as orexigenic neuropeptide Y [NPY] and anorexigenic α-melanocyte–stimulating hormone [α-MSH]) and neurotransmitters (such as anorexigenic serotonin and dopamine) are important in regulating hunger and satiety. Long-term and short-term signals interact, insofar as leptin increases secretion of α-MSH and decreases secretion of NPY. Thus, there are many complex regulatory loops that control the size and number of meals in relationship to the status of body fat stores. [Note: α-MSH, a cleavage product of proopiomelanocortin, binds to the melanocortin-4 receptor (MC4R). Loss-of-function mutations to MC4R are associated with early-onset obesity.]
V. METABOLIC EFFECTS
The primary metabolic effects of obesity include dyslipidemias, glucose intolerance, and insulin resistance expressed primarily in the liver, skeletal muscle, and adipose tissue. These metabolic abnormalities reflect molecular signals originating from the increased mass of adipocytes (see Fig. 25.9, p. 343, and Fig. 26.7). [Note: About 30% of obese individuals do not show these metabolic abnormalities.]
A. Metabolic syndrome
Abdominal obesity is associated with a cluster of metabolic abnormalities (hyperglycemia, insulin resistance, hyperinsulinemia, dyslipidemia [low levels of high-density lipoprotein (HDL) and elevated TAG], and hypertension) that is referred to as the metabolic syndrome (Fig. 26.8). It is a risk factor for CVD and T2D. The low-grade, chronic, systemic inflammation seen with obesity contributes to the pathogenesis of insulin resistance and T2D and likely plays a role in metabolic syndrome. In obesity, adipocytes release proinflammatory mediators such as IL-6 and TNF-α. Additionally, levels of adiponectin, which normally dampens inflammation and sensitizes tissues to insulin, are low.
B. Nonalcoholic liver disease
Obesity is associated with ectopic deposition of TAG in the liver (hepatic steatosis) and results in increased risk for nonalcoholic fatty liver disease ([NAFLD], see p. 343).
VI. OBESITY AND HEALTH
Obesity is correlated with an increased risk of death (Fig. 26.9) and is a risk factor for a number of chronic conditions, including T2D, dyslipidemias, hypertension, CVD, some cancers, gallstones, arthritis, gout, pelvic floor disorders (for example, urinary incontinence), NAFLD, and sleep apnea. The relationship between obesity and associated morbidities is stronger among individuals age <55 years. After age 74 years, there is no longer an association between increased BMI and mortality. [Note: Obesity also has social consequences (for example, stigmatization and discrimination).] Weight loss in obese individuals leads to decreased blood pressure, plasma TAG, and blood glucose levels. HDL increase.
VII. WEIGHT REDUCTION