AP Ch 23 PDF: Obesity and Disorders of Nutrition

## Refeeding Syndrome Refeeding syndrome occurs in severely malnourished individuals when oral or enteral nutritional therapy is initiated. During starvation, loss of body minerals causes the movement of phosphate, magnesium, and potassium ions out of the cells and into the plasma. When refeeding s...

## Refeeding Syndrome Refeeding syndrome occurs in severely malnourished individuals when oral or enteral nutritional therapy is initiated. During starvation, loss of body minerals causes the movement of phosphate, magnesium, and potassium ions out of the cells and into the plasma. When refeeding starts, an increase in insulin levels stimulates the movement of glucose and these ions back into the cells, and the plasma concentration of phosphate, magnesium, and potassium can drop dangerously low levels, causing hypophosphatemia, hypomagnesemia, hypokalemia, hyponatremia, hypocalcemia, and vitamin deficiency. Rapid expansion of the extracellular fluid volume also can occur with carbohydrate refeeding and may cause fluid overload. Hypophosphatemia contributes to alterations in red blood cell shape and function, contributing to increased oxidative stress, and imbalanced hormonal levels. There are no currently used specific treatments for the anorexia of aging, but numerous supportive strategies are used (e.g., improved food appearance, dental and eye care, social stimulation). Death rates have been shown to be higher in those with anorexia of aging and weight loss. ## Summary Review ### Adipose Tissue 1. Adipose tissue provides insulation and tissue support and is the body's major energy reserve, storing triglycerides and glycerol. 2. Adipose tissue is an endocrine organ that secretes hormones called adipokines with autocrine, paracrine, and endocrine actions necessary for metabolic function and immune responses. 3. WAT has a stromal structure that contains macrophages, mast cells, neutrophils, fibroblasts, endothelial cells, blood vessels, nerves, and precursor adipocytes. 4. WAT is the largest fat depot and is located in visceral (central) and subcutaneous (peripheral) sites. It also is located in muscle and bone marrow. 5. White adipocytes store fat as a single lipid droplet or vacuole. 6. With positive energy balance, WAT storage increases by adipocyte hypertrophy (more common in visceral fat) and adipogenesis (more common in subcutaneous fat). 7. Estrogen enhances the deposition of subcutaneous fat compared to visceral fat. 8. BAT has multiple lipid droplets and is rich in mitochondria containing iron, giving BAT a brown color. Exposure to cold, sympathetic activation and release of catecholamines, and activation of T3 generate heat through activation of UCP1 and free fatty acid oxidation (nonshivering thermogenesis). 9. Both neonates and adults have BAT, but not in the amounts of WAT. 10. bAT emerges within WAT with exposure to cold, exercise, and synthetic ligands of PPARy. This is known as the “beiging" of WAT. 11. BAT and bAT both protect against obesity and metabolic syndrome. 12. In muscle, the myokines irisin and fibroblast growth factor-21, respectively, activate BAT and bAT for thermogenesis and protect against obesity. 13. Bone marrow adipose tissue also releases adipokine, and there is crosstalk with osteoclasts to maintain bone structure. ### Obesity 1. Obesity is an epidemic that has occurred worldwide in both adults and children and is the fifth leading cause of death in the United States. Three leading causes of death in the United States are associated with obesity: cardiovascular disease, type 2 diabetes mellitus, and certain cancers. Obesity also increases the risk for numerous other systemic disorders. 2. Obesity is defined as a BMI greater than 30 kg/m² in adults and a BMI greater than or equal to the age- and sex-specific 95th percentile of the 2000 Centers for Disease Control and Prevention growth charts in children and usually results from energy intake exceeding expenditure. 3. Single-gene (rare) and polygenetic disorders and metabolic disorders are associated with obesity, as well gene-environment interactions. 4. Regulation of food intake and energy expenditure is coordinated centrally by the hypothalamus and higher brain centers. Two opposing sets of neurons in the arcuate nucleus of the hypothalamus regulate appetite and energy metabolism: orexigenic neurons, which promote appetite, stimulate eating, and decrease metabolism; and anorexigenic neurons, which suppress appetite, inhibit eating, and increase metabolism. 5. Brain centers related to reward, pleasure, and memory can override hypothalamic control of food intake and satiety, causing increased fat stores by increasing consumption of highly palatable foods. 6. Adipokines and gastrointestinal hormones are altered with obesity and contribute to associated complications. 7. Leptin levels increase with obesity (leptin resistance), promoting overeating, insulin resistance and hyperinsulinemia, and hyperlipidemia, and stimulating adipocyte endothelial cells and macrophages to release inflammatory mediators contributing to the complications of obesity. 8. RBP4 levels are increased in visceral adiposity and promote insulin resistance and hepatic steatosis. ### Adiponectin - Adiponectin levels decrease with obesity, contributing to insulin resistance, inflammation, and hyperlipidemia. - Endocannabinoids are increased in obesity and promote food intake and lipogenesis and inhibit energy expenditure. - Angiotensin I and angiotensin II increase in obesity, promoting vasoconstriction, inflammation, lipogenesis, oxidative stress, and insulin resistance. - Ghrelin increases with obesity and stimulates food intake, promotes release of growth hormone, and stimulates lipogenesis. It also has satiety, vasodilatory, cardioprotective, and antiproliferative effects; its role in obesity is not clear. - Glucagon-like peptide 1 promotes insulin secretion, delays gastric emptying, suppresses appetite, and increases energy expenditure, and is decreased with obesity. - Peptide YY inhibits gastric motility, decreases appetite, and is decreased with obesity. ### Obesity: A State of Chronic Low-grade Inflammation - Obesity is a state of chronic low-grade inflammation caused by expansion of adipocyte macrophages, neutrophils, and lymphocytes that release inflammatory mediators. - The chronic inflammation, alterations in adipokine action, and accelerated lipolysis related to excessive fat contribute to the complications of obesity, particularly insulin resistance, type 2 diabetes mellitus, cardiovascular disease, and cancer. - Changes in the intestinal microbiome also contribute to obesity, but the mechanisms need to be defined. ### Obesity Phenotypes: Visceral or Central obesity - Obesity has two major phenotypes: visceral, or central obesity; and peripheral, or subcutaneous obesity. Visceral obesity has the greatest risk for accelerated lipolysis, chronic inflammation, insulin resistance, and associated complications. ### Treatment of Obesity - Treatment of obesity may include correction of metabolic abnormalities, and individually tailored lifestyle interventions (diets, exercise, behavioral modifications, self-motivation) and psychotherapy. The current most effective treatment for extreme obesity is bariatric surgery. ### New Drugs for Treatment - New drugs are being developed that target specific molecules and will provide a personalized approach to treatment. ## Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder 1. Eating disorders include anorexia nervosa, bulimia nervosa, and binge eating disorder. They are psychogenic disorders that can lead to malnutrition. 2. Complications of chronic and severe eating disorders lead to malnutrition and weight changes, involve all organ systems, and can be life-threatening. Most complications are reversible with treatment. ## Starvation 1. The body responds to short-term starvation with mechanisms to protect protein mass, using the processes of glycogenolysis and gluconeogenesis. Neither of these processes can meet the body's energy needs indefinitely since they deplete stored nutrients. 2. Long-term starvation results in an initial decreased dependence on gluconeogenesis and an increased use of ketone bodies as a cellular energy source, followed by lipolysis in adipose tissue. In the absence of adequate nutrition, long-term starvation results in proteolysis with death resulting from severe alterations in electrolyte balance and loss of renal, pulmonary, and cardiac function. ## Anorexia of Aging 1. Anorexia of aging is a decrease in appetite or food intake in older adults leading to undernutrition and resulting in a decline in function and increased risk for morbidity and mortality. 2. Contributing factors related to aging include diminished sensory functions, poor dentition, decreased gastric emptying, decreased hunger and satiety, effects of medications, social isolation, and neglect.