Endocrinology/Objectives/Lecture 23
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Objectives: 13 - 14 - 15 - 16 - 17 - 18 - 19 - 20 - 21 - 22 - 23 - 24 - 25
Endocrinology of obesity and metabolism
Define obesity.
Obesity is the presence of excess body fat.
Understand how obesity is determined.
The presence of obesity can be determined via the direct measurement of excess body fat, or indirectly via weight and BMI.
Describe how BMI is calculated and why this is important.
BMI is the ratio of mass (in kg) to height (in m) squared. This ratio is relatively constant for a given degree of body fat, so it can be used as a surrogate for direct body fat measurements.
Discuss the different forms of obesity and how they come about.
- Common obesity
- Common obesity is most often caused by overeating, thereby increasing the ratio of energy intake to expenditure. Three significant factors in the etiology of common obesity include increased availability of food, increased portion sizes, and increased caloric intake from fats.
- Maturity-onset obesity
- In some cultures, body weight reflect one's social status: obesity is perceived as power and wealth, while leanness is associated with frailty and servitude. Maturity-onset obesity, at least in these cultures, is therefore often a sign of being powerful and wealthy.
- Hypothalamic obesity
- Results from trauma, malignancy, or inflammatory disease of the hypothalamus, and is often accompanied by other hypothalamic disorders.
- Polycystic ovarian syndrome
- Obesity may predate PCOS and may be part of its etiology.
- Cushing's syndrome
- Hypercortisolism leads to hyperglycemia and chronically elevated insulin levels, which enhance the deposition of adipose tissue (particularly abdominal fat and fat atop the shoulders).
- Hypothyroidism
- Reduced thyroid function may diminish basal metabolic rate and therefore reduce energy expenditure, causing obesity.
- Genetic obesity
- Heritable forms of obesity are known but rare.
Discuss the three components of energy expenditure.
- Resting metabolic rate
- The energy expended during inactivity to drive normal, resting, physiologic processes (e.g. thermal regulation). Accounts for 60-70% of daily energy expenditure.
- Thermogenic processes
- Food consumption, changes in ambient temperature, other hormonal changes or stressors increase energy expenditure over the resting metabolic rate. Accounts for ~10% of daily expenditure.
- Physical activity
- Most variable component, accounting for 20-30% of daily expenditure.
Understand how energy balance and obesity are releated.
Positive energy balance (i.e. when energy intake exceeds energy expenditure) leads to weight gain. Via normal homeostatic mechanisms, this weight gain results in a higher body weight set point associated with even greater energy intake, increased energy expenditure, and increased body mass. Chronic positive energy balance results in obesity.
Describe the three categories of the homeostatic signaling system and the importance of each.
- Satiety signals
- Include cholecystokinin (which regulates meal size by suppressing appetite), bombesins (e.g. GRP, neromedins C & B, which suppress food intake), incretins (secreted by the intestines and elevate insulin, especially in vivo), and glucocorticoids (which alter fat and muscle mass and metabolism).
- Glucostatic signals
- Insulin acts on the hypothalamus to increase sympathetic outflow to brown adipose tissue and therefore diet-induced thermogenesis.
- Lipostatic signals
- Leptin is released by adipose tissue and is an endogenous indicator of body fat content.
Discuss adipocytes as endocrine organs.
- Preadipocytes are macrophage-like and play a role in inflammation.
- Transgenic mice lacking white adipose tissue are hyperglycemic and hyperinsulinemic.
- Adipocytes secrete a number of cytokines, including:
- leptin, an indicator of body fat stores;
- resistin, TNF-α, and IL-6, all of which promote insulin resistance;
- adiponectin and visfatin, adipokines that work synergistically with insulin to enhance glucose uptake by muscle and suppress hepatic gluconeogenesis
Discuss the relationship between obesity and inflammation.
Obesity is characterized by chronic inflammation and elevated production of proinflammatory cytokines (e.g. TNF-α) and acute-phase proteins. It is also common to find infiltration of adipose tissue by macrophages.
Understand leptin and its mechanism of action.
Leptin has effects on short-term feeding behavior via its interactions with blood glucose, cholecystokinin (CCK), plasma amino acids, body temperature, and other hormones. It also has long-term effects by providing a surrogate signal of body fat content. It influences the quantity of food consumed relative to energy expended.
Leptin may also help to regulate the onset of puberty. Abnormally thin females enter puberty later than their peers, indicating that fat may produce a signal (possibly leptin) that regulates reproductive capacity.
Understand resistin and its actions.
Resistin is produced by macrophages and adipocytes and induces insulin resistance. Plasma levels are low during fasting and high in obese individuals. Antiresistin antibodies can reverse insulin resistance. There is controversy over whether elevated resistin is the causative factor in the type of insulin resistance that accompanies obesity (i.e. that seen in type II diabetes mellitus).
