The role of peptide YY in energy homeostasis

The primary purpose of this dissertation is to understand the physiological role of peptide YY (PYY) in response to both acute and chronic changes in energy balance and body weight in women. The specific goals of this dissertation are to characterize the diurnal rhythm of PYY with regard to acute dietary energy intake and explore its role in energy balance, to determine if the proposed opposing actions of ghrelin and PYY at the hypothalamus could be related to their patterns in the peripheral circulation both prior and subsequent to diet- and exercise-induced weight loss, and to determine whether low-energy dense diets might facilitate weight loss through actions on circulating concentrations of ghrelin and PYY. Study 1 was designed to characterize features of the diurnal rhythm of PYY and to explore the role of PYY in energy balance in normal weight premenopausal women. We demonstrated that PYY displays a meal-driven diurnal rhythm and is correlated to resting metabolic rate, a major contributor to energy expenditure. Thus, PYY varies in accordance with energy content and RMR, supporting a role for PYY in energy balance modulation. Study 2 was designed to determine if the proposed opposing actions of ghrelin and PYY at the hypothalamus could be related to their patterns in the peripheral circulation during a period of weight stability in nonexercising, normal weight premenopausal women. We demonstrated that circulating concentrations of PYY were inversely associated with ghrelin over an entire 24 hour period. We concluded that these data provide evidence that PYY may contribute to the modulation of the secretion of ghrelin in normal weight, premenopausal women over a 24 hour period which supports similar inferences from experimental studies in animals and humans. The purpose of Study 3 was designed to determine if diet- and exercise-induced weight loss would alter the 24-hour profile of total circulating PYY and to determine if the association between 24-hour circulating concentrations of PYY and ghrelin observed during a period of weight stability (study 2) will be altered subsequent to a period of diet- and exercise-induced weight loss in normal weight, premenopausal women. We demonstrated that no change occurred in the 24-hour profile of total circulating PYY subsequent to diet- and exercise-induced weight loss and that the association observed at baseline between ghrelin and PYY (Study 2) was weakened subsequent to diet- and exercise-induced weight loss where circulating concentrations of ghrelin increased despite administration of exactly the same calorie and macronutrient content of meals during the 24-hour analyses. We also created a variable to illustrate an index of hormonal exposure in an attempt to demonstrate the potential predominance of ghrelin over PYY in the circulation in response to weight loss. To accomplish this, we calculated the ghrelin/PYY ratio over 24 hours at baseline and the post intervention time points. The lunch ghrelin/PYY mean was significantly higher at post intervention and trends toward significant increases were observed in the dinner and nocturnal ghrelin/PYY means demonstrating that the time frame during which uncoupling of the ghrelin and PYY profiles occurred was mainly throughout the lunch to dinner time period. This uncoupling may represent periods during which there is a predominance of ghrelin over PYY in the circulation subsequent to weight loss which may promote weight regain. The purpose of Study 4 was to determine whether low-energy dense diets might facilitate weight loss through actions on circulating concentrations of ghrelin and PYY, independent of the influence of psychosocial measures of dietary restraint, disinhibition, and tendency toward hunger in overweight and obese women. We demonstrated that reductions in dietary energy density may promote weight maintenance after a period of weight loss by opposing increases in ghrelin in response to an energy deficit that can lead to weight regain, as well as by promoting increases in circulating concentrations of the satiety hormone PYY. Overall, ghrelin and PYY are likely important factors involved in the response to, as well as the modulation of body weight regulation in women. As well, ghrelin and PYY may modulate on another during a period of weight stability, but that association may be altered in a state of energy imbalance where the 24-hour profile of ghrelin, but not PYY is elevated. Lastly, low energy dense diets may impact circulating concentrations of ghrelin and PYY in such a manner as to promote satiety and prevent weight re-gain subsequent to a period of weight loss.