Fifty obese adults without diabetes mellitus are enrolled in a 10-week weight loss program. The program includes a low-calorie diet and moderate-intensity exercise for at least 150 minutes per week. The study subjects who are adherent to the regimen lose an average of 7 kg (15.5 lb) at the end of 10 weeks. Venous blood samples to study biochemical changes induced by weight loss are taken at the start of the trial and at the 10-week follow-up visit. Which of the following hormonal changes are likely to occur during the course of the study?

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11ec160b_3cb7_c39f_9249_1578f876c3f0_MD0001_00 Energy homeostasis and body fat content are regulated by a complex network of hormones. Prominent hormones involved in weight regulation include: Ghrelin: Produced primarily in the stomach in response to fasting, ghrelin stimulates appetite and promotes weight gain. Leptin: Produced primarily by fat cells in response to short-term food intake and long-term adequacy of fat stores, leptin acts on the hypothalamus to decrease appetite (obesity blunts this action). During fasting states, leptin levels fall. Insulin: Produced by pancreatic beta cells in response to high blood glucose levels, insulin acts on the CNS to decrease appetite, in addition to its effects on glucose metabolism. Levels are higher and effects are blunted in obesity (insulin resistance); weight loss is associated with greater insulin sensitivity and lower insulin levels. Caloric restriction and falling fat stores, as in these study subjects, lead to increased ghrelin levels along with decreased insulin and leptin levels. This causes an increase in appetite and, typically, regain of weight. The effect can last up to a year or more and accounts for much of the difficulty patients have in maintaining short-term weight loss. (Choice B) Certain bariatric procedures that alter stomach capacity (eg, sleeve gastrectomy) can induce weight loss with decreased ghrelin production (may reduce weight loss-associated appetite stimulation). However, dietary modification and exercise alone would lead to increased ghrelin secretion. (Choice C) Overeating and weight gain suppress ghrelin secretion and increase secretion of leptin and insulin. (Choice D) HIV-associated lipodystrophy is an alteration in fat distribution, most often seen in patients receiving highly active antiretroviral therapy. Numerous metabolic abnormalities have been seen in this disorder, including increased insulin levels, increased ghrelin, and decreased leptin secretion. (Choice E) Fasting states that stimulate ghrelin and suppress insulin secretion generally lead to lower, not higher, leptin levels. Educational objective: Ghrelin stimulates appetite and promotes weight gain. Leptin and insulin act in the CNS to decrease appetite. Caloric restriction leads to increased ghrelin levels along with decreased insulin and leptin levels, causing an increase in appetite that can make it difficult to maintain weight loss. __________ References: Long-term persistence of hormonal adaptations to weight loss. (http://www.ncbi.nlm.nih.gov/pubmed/22029981)

Fifty Obese Adults Without Diabetes Mellitus Are Enrolled in a 10-Week