June 12, 2007; doi:10.1152/ajpendo.00153.2007 infusions have been reported to reduce energy intake (EI) in humans, whereas few studies exist on effects of PYY1-36. The aim of the present study was to examine effects of subcutaneous (sc) injections of PYY 1-36 and PYY3-36 on appetite, ad libitum EI, plasma concentrations of PYY and free fatty acids (FFA) in obese males. Twenty-four males (BMI 27-40 kg/m 2 ) were randomly assigned to two groups receiving sc injections of either PYY 1-36 or PYY3-36 in a blinded, placebo-controlled, dose-escalating, cross-over study. Subjects were studied 5 days in succession, with escalating doses of PYY [saline, 50, 100, 150, and 200 pmol PYY1-36/kg lean body mass (LBM)], or 25, 50, 75, and 100 pmol PYY 3-36/kg LBM), respectively. PYY injections resulted in dose-dependent increases in plasma PYY levels but no effect on EI in either the PYY 1-36 or the PYY3-36 group. However, increasing doses of PYY 3-36, but not PYY1-36, resulted in increased ratings of satiety and decreased ratings of hunger, thirst, and prospective food consumption. Although not dose dependently, significant elevation of plasma FFA was seen after injection of PYY 3-36, but not PYY1-36. Although sc administration of PYY was well tolerated, it remains to be determined whether high-dose PYY 3-36 is sufficient in reducing EI in long-term trials, and if so, whether the reduction in EI occurs without nausea. PYY 1-36 is unlikely to be important in regulating energy intake. The PYY 3-36 administrations caused a non-dose-dependent mobilization of FFA, likely through a direct effect. peptide YY; lipolysis; catecholamine; hunger; satiety IT IS WELL KNOWN that we are in the midst of an obesity epidemic with the associated pathological features resulting in serious consequences for human health and health-related economics. The search for potent antiobesity drug targets is therefore important and has in recent years focused on peptides altering human appetite. Peptide YY (PYY) is an endogenous 36-amino acid peptide found in endocrine cells of the gastrointestinal mucosa and in the circulation (1). It is released postprandially as PYY 1-36 and cleaved by dipeptidyl peptidase-IV to yield PYY 3-36 (9, 10). PYY 3-36 is believed to access the arcuate nucleus via systemic circulation and to act on the presynaptic inhibitory Y2 receptor of neuropeptide Y (NPY) neurons (3). PYY 1-36 has affinity for the Y1, Y2, and Y5 receptors, whereas PYY 3-36 binds more selectively to the Y2 receptor and with lower affinity to the Y5 receptor (17).Human PYY 3-36 intravenous (iv) infusion studies have demonstrated dose-dependent (4, 12) decreases in energy intake (EI) of 23-36% at subsequent meals following 90 min of infusion at a rate of 0.8 pmol⅐kg Ϫ1 ⅐min Ϫ1 (2-4, 12). The quantity of this suppression of food intake and the fact that the effect has been shown to last for 12 h (2, 3), makes PYY 3-36 a promising antiobesity drug target. However, side effects in the form of nausea, vomiting, abdominal discomfort, fullness, and sweating have a...

Women's weight and body composition is significantly influenced by the female sex-steroid hormones. Levels of these hormones fluctuate in a defined manner throughout the menstrual cycle and interact to modulate energy homeostasis. This paper reviews the scientific literature on the relationship between hormonal changes across the menstrual cycle and components of energy balance, with the aim of clarifying whether this influences weight loss in women. In the luteal phase of the menstrual cycle it appears that women's energy intake and energy expenditure are increased and they experience more frequent cravings for foods, particularly those high in carbohydrate and fat, than during the follicular phase. This suggests that the potential of the underlying physiology related to each phase of the menstrual cycle may be worth considering as an element in strategies to optimize weight loss. Studies are needed to assess the weight loss outcome of tailoring dietary recommendations and the degree of energy restriction to each menstrual phase throughout a weight management program, taking these preliminary findings into account.