Harrison's Internal Medicine Chapter 41. Weight Loss Weight Loss: Introduction Significant unintentional weight loss in a previously healthy individual is often a harbinger of underlying systemic disease. During the routine medical examination, changes in weight should always be assessed; loss of 5% of body weight over 6–12 months should prompt further evaluation. Physiology of Weight Regulation The normal individual maintains body weight at a remarkably stable "set point," given the wide variation in daily caloric intake and level of activity. Because of the physiologic importance of maintaining energy stores, voluntary weight loss is difficult to achieve and sustain. Appetite and metabolism are regulated. | Chapter 041. Weight Loss Part 1 Harrison s Internal Medicine Chapter 41. Weight Loss Weight Loss Introduction Significant unintentional weight loss in a previously healthy individual is often a harbinger of underlying systemic disease. During the routine medical examination changes in weight should always be assessed loss of 5 of body weight over 6-12 months should prompt further evaluation. Physiology of Weight Regulation The normal individual maintains body weight at a remarkably stable set point given the wide variation in daily caloric intake and level of activity. Because of the physiologic importance of maintaining energy stores voluntary weight loss is difficult to achieve and sustain. Appetite and metabolism are regulated by an intricate network of neural and hormonal factors. The hypothalamic feeding and satiety centers play a central role in these processes Chap. 74 . Neuropeptides such as corticotropin-releasing hormone CRH a-melanocyte-stimulating hormone a-MSH and cocaine- and amphetamine-related transcript CART induce anorexia by acting centrally on satiety centers. The gastrointestinal peptides ghrelin glucagon somatostatin and cholecystokinin signal satiety and thus decrease food intake. Hypoglycemia suppresses insulin reducing glucose utilization and inhibiting the satiety center. Leptin is produced by adipose tissue and it plays a central role in the longterm maintenance of weight homeostasis by acting on the hypothalamus to decrease food intake and increase energy expenditure Chap. 74 . Leptin suppresses expression of hypothalamic neuropeptide Y a potent appetite stimulatory peptide and it increases the expression of a-MSH which acts through the MC4R melanocortin receptor to decrease appetite. Thus leptin activates a series of downstream neural pathways that alter food-seeking behavior and metabolism. Leptin deficiency which occurs in conjunction with the loss of adipose tissue stimulates appetite and induces adaptive responses including .
