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Michael Zemel PhD: University of Wisconsin - Madison 229 Jessie Harris Building |
Keywords:
Adipocyte, agouti, calcium, insulin, obesity, pancreas, sulfonylurea
Research Area:
Regulation of intracellular Ca2+ in adipocytes, and intracellular Ca2+ regulation of adipocyte genes controlling lipid metabolism.
Description of Research:
Research in my laboratory focuses on alterations in intracellular calcium ([Ca2+]i) transport and metabolism which increase the susceptibility to obesity, diabetes and hypertension. Most recently, we have been working to identify the mechanism of action of the agouti gene. Over-expression of this gene in the mouse results in a syndrome of obesity and insulin resistance. We have demonstrated that the agouti gene product stimulates Ca2+ influx and an increase in steady state [Ca2+]i in several types of cells, including skeletal muscle, vascular smooth muscle and adipocytes, with consequences for both obesity and diabetes. Further, we have found that, in the human adipocyte, the agouti gene product inhibits lipolysis and stimulates lipogenesis in a Ca2+-dependent manner and that modulation of Ca2+ channel activity may have a significant effect on lipid accumulation. Similarly, in the human pancreatic islet, we have found insulin to be a potent stimulus for Ca2+-dependent insulin release. This work demonstrates that Ca2+ channels, and the receptors which regulate them, are important targets for the development of preventive and therapeutic strategies in obesity and diabetes. Based on this work, we have recently identified a human adipocyte sulfonylurea receptor and a putative L-type Ca2+ channel, both of which regulate lipogenic genes, as well as novel Ca2+-mediated system which modulate adipocyte hormone sensitive lipase and adipocyte uncoupling protein expression. Consequently, research in my laboratory is now focused largely on understanding the molecular and endocrine regulation of these targets as well as further investigations in the role of the agouti gene in human obesity and insulin resistance. We are presently focusing on the role of calcitrophic hormones, which are responsive to dietary calcium and which modulate cellular Ca2+ flux , in modulating adipocyte metabolism.
Selected Publications:
- Morris, K.L., Zemel, M. B., Effect of Dietary Carbohydrate Source on the Development of Obesity in Agouti Transgenic Mice, Obesity Research, 13, 21-25, 2005
- Zemel, M.B., Richards, J., Mathis, S., Milstead, A., Gebhardt, L., Silva, E., Dairy Augmentation of Total and Central Fat Loss in Obese Subjects, International Journal of Obesity, 29, 391-397, 2005
- Morris, K.L., Zemel, M.B., 1,25-dihydroxyvitamin D-3 Modulation of Adipocyte Glucocorticoid Function, Obesity Research, 13, 670-677, 2005
- Zemel, M.B., Calcium Regulation of Adiposity, Obesity Research, 13, 192-193, 2005
- Zemel, M.B., Richards, J., Milstead, A., Campbell, P., Effects of Calcium and Diary on Body Composition and Weight Loss in African-American Adults, Obesity Research, 13, 1218-1225, 2005
- Thompson, W.G., Holdman, N.R., Janzow, D.J., Slezak, J.M., Morris, K.L., Zemel, M.B., Effect of Energy-reduced Diets High in Dairy Products and Fiber on Weight Loss in Obese Adults, Obesity Research, 13, 1344-1353, 2005
- Zemel, M.B., Role of Dairy in Weight Management, J. Am. Coll. Nutr., In Press, 2005
- Sun X and Zemel MB, Calcium and dairy inhibit weight and fat regain during ad libitum consumption following energy restriction in aP2-agouti transgenic mice, Journal of Nutrition, 134, 3054-3060, Nov 2004
- Sun X and Zemel MB, Role of Uncoupling Protein 2 (UCP2) Expression and 1alpha, 25-Dihydroxyvitamin D3 in Modulating Adipocyte Apoptosis, FASEB Journal, 18, 1430-1432, Oct 2004