Obesity is a disease of literally and figuratively enormous proportions. We have chosen a model of naturally occurring obesity-- photoperiod-induced seasonal obesity in Siberian hamsters (Phodopus sungorus sungorus). Siberian hamsters are naturally obese when housed in long """"""""summer- like"""""""" days (LDs) and lose body mass, nearly exclusively as body fat, when exposed to short, """"""""winter-like"""""""" days. After prolonged SD exposure and/or with increasing daylengths, body and lipid mass increase to their previous obese LD levels. Thus, the obesity is reversible.
Three Specific Aims (SA) are proposed, each represented by a set of experiments. 1: What is the functional role of the sympathetic nervous system (SNS) in the photoperiod-induced differential decrease in white adipose tissue (WAT) mass and what is its CNS neuroanatomical substrate? We have demonstrated previously that a relatively separate direct SNS innervation exists for WAT pads. Experiments are designed to test further the separate neurologies associated with the SNS innervation of WAT and the function of this innervation. Therefore, we will answer the questions: 1) Can the SD-induced decreases in body fat occur independently of the SNS innervation of WAT? and 2) Does the relatively separate SNS innervation of WAT converge in the CNS? SA 2: What is the extent of the sensory innervation of WAT and what is its function in the photoperiod-induced changes in body fat? We have extended the initial observation of sensory innervation of WAT in laboratory rats to Siberian hamsters. However, in both studies, only subcutaneous WAT was tested for sensory innervation. In addition, we do not know the neurotransmitter phenotypes of these neurons, nor their function. Therefore, we will answer the questions: 1) What is the extent of the sensory innervation of WAT and what are the neurotransmitter phenotypes of the sensory neurons innervating this tissue? 2) What is the functional role of the sensory innervation of WAT in the SD-induced decreases in body fat? and 3) Is the SNS drive on the tissue increased following sensory denervation? SA 3: What are the neural contributions to total body fat regulation? We have shown that total body fat appears to be regulated based on the results of lipectomy experiments in Siberian hamsters; however, we do not know the mechanism underlying this regulation. Therefore, we will answer the following questions: 1) Is the SNS drive on the fat pads that show compensatory increases in fat pad mass decreased following lipectomy? 2) What is the role of the SNS innervation of WAT in the regulation of total body fat following lipectomy? and 3) What is the role of the sensory innervation of WAT in the regulation of total body fat by lipectomized hamsters? The results of these experiments should provide new information about the importance of the neural innervation of WAT, the regulation of total body fat and in the photoperiodic control of seasonal body fat cycles. In addition, insight into the fundamental processes involved in the development, maintenance and reversal of obesity also should occur.
Showing the most recent 10 out of 64 publications
