Caroline Apovian, M.D., Director of the Center for Nutrition and Weight Management, and Associate Professor of Medicine, has been engaged in clinical studies related to various dietary and drug effects on weight reduction. These studies include weight loss in subjects on a VLCD and sibutramine versus placebo; a prospective study of risk factors for heart disease in subjects pre- and post-gastric bypass surgery; an investigation of an MCT oil-based liquid diet and the effects on weight loss; endothelial function in obese subjects on a weight-loss program; hypocaloric-hyperprotein enteral nutrition versus relative normocaloric enteral nutrition in critically ill medical patients; interventions to enhance adherence to obesity guidelines by providing four-hour workshops on obesity treatment to primary care physicians with patient chart follow-up; and a randomized, controlled study to examine the relationship between changes in plasma GIP levels and other gastrointestinal peptides following gastric bypass surgery in obese patients.
Bench research being done by Nawfal Istfan, M.D., Ph.D., Associate Professor of Medicine, in his National Institutes of Health (NIH)-funded laboratory focuses on the mechanisms of S-phase prolongation by fish oil. His main objective is to test the hypothesis that omega-3 fatty acids alter the nuclear structure of mammalian cells in a manner that lengthens DNA replication time. The proposed mechanism involves the complex process of organization of replication foci at specific DNA sites.
Obesity, particularly abdominal obesity, confers increased risk for cardiovascular disease, type 2 diabetes, osteoarthritis, stroke and cancer. The long-term goal of research in the laboratory of Susan K. Fried, Ph.D. is to understand how fat deposition in different anatomical depots is regulated, and why abdominal obesity is associated with metabolic abnormalities. She is currently engaged in several projects that should shed light on these questions:
Regulation of leptin production: Adipocytes are now recognized as endocrine cells that produce a variety of hormones, including leptin, interleukin-6, and adiponectin. However, very little is known about the mechanisms that regulate the synthesis and secretion of adipose hormones (adipokines). We have focused our attention on leptin, an adipocyte hormone that regulates metabolism and appetite and is centrally involved in the regulation of body weight. Leptin production is increased in proportion to the amount of fat stored in the adipocyte. In addition, serum leptin levels change independent of adiposity, in response to changes in nutritional status. Our recent studies using human adipose tissue placed in organ culture and a rat model indicate that the nutritional regulation of leptin production is regulated, at least in part, by insulin, glucocorticoids, catecholamines and cytokines (Figure 1). Using metabolic labeling and immunopreciptation methods to monitor rates of leptin synthesis, turnover and secretion, we have demonstrated that pre- and post-transcriptional mechanisms are involved. Reporter assays show that elements within the 5’ UTR of leptin stimulates, while the 3’UTR inhibits translation. The insulin stimulation of leptin mRNA translation requires both UTRs. Current studies are investigating the cis elements and transacting factors that mediate the nutritional regulation of leptin mRNA translation.
Depot differences in adipose tissue metabolism: We find significant differences in cytokine production in visceral (omental) adipose tissue. Interestingly, we find these cytokines are expressed mainly in stromal cells, not adipocytes. We are currently studying the hormonal regulation of cytokine production (TNFa, IL6 and 8) in human omental vs subcutaneous adipose tissue, as well as the metabolic effects of these cytokines on adipocyte metabolism and leptin production.
Also in the Center for Nutrition and Weight Management, Thomas Moore, M.D., Professor of Medicine, is testing a web-based nutrition (the DASH diet) and exercise education program, offered to the employees of EMC Corp.