PHOTOPERIODIC CONTROL OF OBESITY

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Obesity is a disease of figuratively and literally enormous proportions. Women with male-type body fat distribution exhibit an exaggeration of the secondary health consequences of obesity such as increased probability of cardiovascular disease, stroke, non-insulin dependent diabetes mellitus and carcinomas. The study of traditional animal models of human obesity have left considerable gaps in our knowledge of the mechanisms underlying body fat distribution and deposition. It has been suggested that species that show naturally-occurring changes in body and lipid mass cycles may be valuable in the study of obesity. The Siberian hamster (Phodopus sungorus sungorus) is one such species. In long, summer-like photoperiods they are naturally obese; however, when they are transferred to short, winter-like photoperiods they lose body mass, nearly exclusively as body fat. After prolonged short day exposure and/or with increasing daylengths, body and lipid mass increase to their previous obese state. Thus, this is a reversible, naturally-occurring obesity that is convenient to study because it is completely under the control of the daylength. The overall purpose of the proposed research is to examine the photoperiod-induced control of regional fat pad-specific changes in lipid storage and how this process contributes to the seasonally appropriate 'regulation' of total body fat. In addition, the impact of this regulation on energy balance (i.e., food intake and thermogenesis) will be examined. Three specific aims are proposed, each represented by a set of experiments. Specific Aim 1: Are the photoperiodic changes in total body fat 'regulated' and what mechanisms underlie this process? Levels of body fat will be manipulated to see if seasonally appropriate adjustments are made to these challenges. Body fat compensation, neural and hormonal influences and changes in energy input and output will be assessed. Specific Aim 2: What hormones or autocrine/paracrine factors mediate the photoperiodic control of body and lipid mass, lipid metabolism and energy balance? Several hormones or autocrine/paracrine factors affected by the photoperiod will be examined for their influence on body and lipid mass (fat distribution), lipid metabolism and energy balance. Specific Aim 3: What is the role of the sympathetic nervous system (SNS) in the photoperiodic control of body and lipid mass, lipid metabolism, an energy balance? The type and extent of the innervation of white adipose tissue (WAT) will be examined using neuronal tract-tracing techniques. Confirmation of innervation and tests of its function will be done using selective surgical denervation. Photoperiod-induced, region-specific changes in the control of lipolysis (fat breakdown) in WAT pads by the SNS will be examined and will include measurement of changes in adipocyte adrenergic receptors, norepinephrine turnover, and in vivo and in vitro lipolytic rates. This multidisciplinary approach should provide new information about the photoperiodic influences on body and lipid mass, lipid metabolism and energy balance that may reflect fundamental processes in the development, maintenance and reversal of obesity.