2. BODY WEIGHT REGULATION
• The body weight of most individuals tends to be relatively stable over time. Each individual has a
biologically predetermined “set point” for body weight
• The body attempts to add to adipose stores when the body weight falls below the set point and to lose
adipose from stores when the body weight rises above the set point.
• Thus, the body defends the set point with weight loss, appetite increases and energy expenditure falls,
whereas with overfeeding, appetite falls and energy expenditure may slightly increase
• A. Genetic contributions: genetic mechanisms play a major role in determining body weight
• 1. Biologic origin: The importance of genetics as a determinant of obesity is indicated by the observation
that children who are adopted usually show a body weight that correlates with their biologic rather than
adoptive parents. Furthermore, identical twins have very similar BMI, whether reared together or apart,
and their BMI are more similar than those of nonidentical, dizygotic twins
• 2. Mutations: Rare, single gene mutations can cause human obesity. For example, mutations in the gene
for leptin (causing decreased production) or its receptor (decreased function) result in hyperphagia
(increased appetite for and consumption of food) and severe obesity underscoring the importance of the
leptin system in regulating human body weight
3. ENVIRONMENTAL AND BEHAVIORAL
CONTRIBUTIONS
• environmental factors, such as the
• ready availability of palatable, energy-dense foods, play a role.
• sedentary lifestyles decrease physical activity and enhance the tendency to gain weight.
• Eating behaviors, such as portion size, variety of foods consumed, an individual’s food
preferences,
• and the number of people present during eating, also influence food consumption
4. MOLECULAR INFLUENCES
• Obesity results when energy (caloric) intake exceeds energy expenditure.
• However, the mechanism underlying this imbalance involves a complex interaction of
biochemical, neurologic, environmental, and psychologic factors.
• The basic neural and humoral pathways that regulate appetite, energy expenditure, and
body weight involve systems that regulate short-term food intake (meal to meal), and
signals for the long-term (day to day, week to week, year to year) regulation of body weight
5. A. LONG-TERM SIGNALS
• Long-term signals reflect the status of fat (TAG) stores.
• 1. Leptin: Leptin is an adipocyte peptide hormone that is made and secreted in proportion to the
size of fat stores. It acts on the brain to regulate food intake and energy expenditure. When we
consume more calories than we need, body fat increases, and leptin production by adipocytes
increases
• The body adapts by increasing energy use (increasing activity) and decreasing appetite (an
anorexigenic effect). When body fat decreases, the opposite effects occur
• 2. Insulin: Obese individuals are also hyperinsulinemic. Like leptin, insulin acts on hypothalamic
neurons to dampen appetite. [Note: Obesity is associated with insulin resistance
6. B. SHORT-TERM SIGNAL
• 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
7.
8. 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
• 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
It is a risk factor for CVD and T2D
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
9. OBESITY AND HEALTH
• Obesity is correlated with an increased risk of death 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
• 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
10. WEIGHT REDUCTION
• Weight reduction can help reduce the complications of obesity. To achieve weight reduction, the obese patient must decrease
energy intake or increase energy expenditure
• Typically, a plan for weight reduction combines dietary change; increased physical activity; and behavioral modification, which
can include nutrition education and meal planning, recording food intake through food diaries, modifying factors that lead to
overeating, and relearning cues to satiety
• Once weight loss is achieved, weight maintenance is a separate process that requires vigilance because the majority of
patients regain weight after they stop their weight-loss efforts.
• Weight reduction can be achieved by following strategies
A. Caloric restriction
B. Physical activity
C. Pharmacologic treatment
D. Surgical treatment
11. A. CALORIC RESTRICTION
• Dieting is the most commonly practiced approach to weight control. Because 1 lb of adipose
tissue corresponds to ~3,500 kcal, the effect that caloric restriction will have on the amount of
adipose tissue can be estimated
• Caloric restriction is ineffective over the long term for many individuals. Over 90% of people who
attempt to lose weight regain the lost weight when dietary intervention is suspended
• Nonetheless, although few individuals will reach their ideal weight with treatment, weight losses
of 10% of body weight over a 6-month period often reduce blood pressure and lipid levels and
enhance control of T2D
• Weight loss on calorie-restricted diets is determined primarily by caloric intake and not nutrient
composition. [Note: However, compositional aspects can affect glycemic control and the blood
lipid profile.]
12. B. PHYSICAL ACTIVITY
• An increase in physical activity can create an energy deficit. Although adding exercise to a
hypocaloric regimen may not produce a greater weight loss initially, exercise is a key
component of programs directed at maintaining weight loss
• physical activity increases cardiopulmonary fitness and reduces the risk of CVD,
independent of weight loss
• Persons who combine caloric restriction and exercise with behavioral treatment may
expect to lose ~5%–10% of initial body weight over a period of 4–6 months
• Studies show that individuals who maintain their exercise program regain less weight after
their initial weight loss
13. C. PHARMACOLOGIC TREATMENT
• The U.S. Food and Drug Administration has approved several weight-loss medications for use
in adults.
• They include
orlistat (decreases absorption of dietary fat),
lorcaserin and phentermine in combination with topiramate (promote satiety through serotonin
signaling),
liraglutide (decreases appetite by activating the glucagon-like peptide 1 receptor),
buproprion in combiation with naltrexone (increase metabolism by increasing norepinephrine)
• Their effects on weight reduction tend to be modest
14. D. SURGICAL TREATMENT
• Gastric bypass and restriction surgeries are effective in causing weight loss in severely
obese individuals
• These operations greatly improve glycemic control in morbidly obese diabetic individuals
• Implantation of a device that electrically stimulates the vagus nerve to decrease food
intake has been approved
