How do leptin and ghrelin work to control food intake? What role does leptin play in genetic causes of obesity?

Question

What will be an ideal response?

Answer 1

Researchers have identified an obesity gene, called ob, which is expressed primarily in the adipose tissue and codes for the protein leptin. Leptin acts as a hormone, primarily in the hypothalamus. Leptin maintains homeostasis by regulating food intake and energy expenditure in response to adipose tissue. When body fat increases, leptin increases—which suppresses appetite. When body fat decreases, leptin decreases—which stimulates appetite and suppresses energy expenditure.
Although extremely rare, a genetic deficiency of leptin or genetic mutation of its receptor has been identified in human beings as well. Extremely obese children with barely detectable blood levels of leptin have little appetite control; they are constantly hungry and eat considerably more than their siblings or peers. Given daily injections of leptin, these children lose a substantial amount of weight, confirming leptin’s role in regulating appetite and body weight.
Very few obese people have a leptin deficiency, however. In fact, leptin levels increase as BMI increases. Leptin rises but fails to suppress appetite or enhance energy expenditure—a condition researchers describe as leptin resistance. With weight loss, leptin levels decline, which reduces satiation and challenges weight loss maintenance; leptin injections effectively increase satiation after weight loss.
Another protein, known as ghrelin, also acts as a hormone primarily in the hypothalamus. In contrast to leptin, ghrelin is secreted primarily by the stomach cells and promotes eating and weight gain by increasing smell sensitivity, stimulating appetite, and promoting efficient energy storage.
Ghrelin triggers the desire to eat. Blood levels of ghrelin typically rise before and fall after a meal—reflecting the hunger and satiety that precede and follow eating. On average, ghrelin levels are high whenever the body is in negative energy balance, as occurs during low-kcalorie diets, for example. This response may help explain why weight loss is so difficult to maintain. Weight loss is more successful with exercise and after gastric bypass surgery, in part because ghrelin levels are relatively low. Ghrelin levels decline again whenever the body is in positive energy balance, as occurs with weight gains.
Some research indicates that ghrelin also promotes sleep. Interestingly, a lack of sleep increases the hunger hormone ghrelin and decreases the satiety hormone leptin—which may help to explain the association between inadequate sleep and overweight.