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Home » ... » - Faculty » Faculty Pages » Ntambi, James M. |
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Ntambi, James M.
 James M. Ntambi
Katherine Berns Von Donk Steenbock Professor
Research Area: Gene Regulation. Fat Cell Differentiation. Fat cell differentiation and dietary and hormonal regulation of gene expression.
Home Dept: Biochemistry, College of Agricultural and Life Sciences
Affiliated Depts: Molecular and Environmental Toxicology and Nutritional Sciences, College of Agricultural and Life Sciences
Address
415B Biochemistry Addition
433 Babcock Drive
Madison, WI 53706-1544
608/265-3700 - Email
Patents
2006-Methods and compositions using stearoyl-CoA desaturase to identify triglyceride reducing..
Research
Cellular differentiation and hormonal and dietary regulation of the stearoyl-CoA desaturase (SCD) genes
Our laboratory is intersted in the molecular mechanisms of cellular differentiation and gene expression. To address the problem, we are studying a cell line of mouse fibroblasts (preadipocytes) that undergo differentiation to adipocytes in cell culture. During the differentiation process the levels of expression of a large number of adipocyte-specific genes increase in a coordinate fashion. One of these genes encodes stearoyl-CoA desaturase, an enzyme that catalyzes the de novo biosynthesis of oleate and palmitoleate, which are the major monounsaturated fatty acids found in triglycerides of fat cells. We are using molecular biology approaches to characterize the mechanisms that regulate the expression of the stearoyl-CoA desaturase gene (SCD); the objective being to determine the molecular events which define the differentiation process.
In addition to acting as a marker of preadipocyte differentiation, the stearoyl-CoA desaturase plays an important role in lipid metabolism and consequently we have carried out studies aimed at defining the role of fatty acids, cholesterol, carbohydrates, peroxisome proliferators, temperature and hormones in the regulation of the stearoyl-CoA desaturase gene in different tissues.
To address further the physiological role of the SCD gene in lipid metabolism, we generated a mouse with a targeted disruption of the SCD gene. This animal model has so far enabled us to demonstrate that monounsaturated fatty acids the products of SCD are required in the de novo biosynthesis of triglycerides, phospholipids, cholesterol esters and wax esters.
Understanding general cellular differentiation, has become an area of intense research because of the far-reaching implications of lipid metabolism and regulation on human diseases such as obesity, diabetes, cancer, and heart disease. Fat deposition in obese individuals is aberrant in comparison to non-obese individuals. This distinction is probably genetic, and may involve overexpression of key enzymes such as SCD and/or transcription factors. The ties between SCD expression, adiposity and disease provide motivation to elucidate the mechanisms involved in the control of this process. With the characterization and understanding of the key regulatory genes involved in lipid metabolism, manipulation of fat deposition and control of many metabolic disorders may be possible.
We recently cloned the human homologue of stearoyl-CoA desaturase gene. The availability of this gene will enable us to study issues that affect human health.
Publications- Sampath, H. and Ntambi, J. M. Polyunsaturated fatty acids and regulation of gene expression. In: Fatty Acids in Foods and Their Health Implications, C. K. Chow, ed., Marcel Dekker Inc., N.Y.,(2007)
- Harini Sampath, Makoto Miyazaki, Agnieszka Dobrzyn and James M. Ntambi Stearoyl CoA desaturase-1 Mediates the Prolipogenic effects of dietary saturated fat JBC (2007)
- Marwah, A., Gomez, F. E., Marwah, P, Ntambi, J. M., Fox, B. G. and Lardy, H. Redox reactions of dehydroepiandrosterone and its metabolites in differentiating 3T3-L1 adipocytes. A liquid chromatographic-mass spectrometric study. Arch. Biochem. Biophys (2007)
- Flowers, M. T., Groen, A. K., Oler, A., Gray-Keller, M. P., Choi, Y., Schueler, K. L., Richards, o. C., Lan, H., Miyazaki, M., Kuipers, F., Kendziorski, C., Ntambi, J. M. and Attie, A. D. Cholesterol and hypercholesterolemia in SCD1-deficient mice fed a low-far, high-carbohydrate diet. J Lipid Res. 2006 Dec;47(12):2668-80
- Chu, K., Miyazaki, M., Man, W. C. and Ntambi, J. M. Stearoyl-coenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation. Mol. Cell. Biol. 26, 6786-6798 (2006).
- McGinnis, J. M., Birt, D. F., Brannon, P. M., Carroll, R. J., Gibbons, R. D., Hazzard, W. R., Kamerow, D. B., Levin, B., Ntambi, J. M., Paneth, N., Rogers, D., Saftlas, A. F. and Vaughan, W. National Institutes of Health State-of-the-Science Conference Statement: Multivitamin/Mineral Supplements and Chronic Disease Prevention. Annals of Internal Medicine, Vol. 145, Issue No. 5, pp. 364-371 (2006).
- Man, W. C., Miyazaki, M., Chu, K. and Ntambi, J. M. Co-localization of SCD1 and DGAT2: implying preference for endogenous monounsaturated fatty acids in triglyceride synthesis. J. Lipid Res. 47, 1928-1939 (2006).
- Sampath, H. and Ntambi, J. M. Regulation of gene expression by polyunsaturated fatty acids. Heart and Metabolism, 2006: 32:32-35
- Biddinger, S. B., Miyazaki, M., Boucher, J., Ntambi, J. M. and Kahn, C. R. Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element-binding protein-1c. Diabetes 55, 2032-2041 (2006).
- Flowers, M. T., Miyazaki, M., Liu, X. and Ntambi, J. M. Probing the role of stearoyl-CoA desaturase-1 in hepatic insulin resistance. J. Clin. Invest. 116, 1478-1481 (2006).
- Ntambi, J. M. Lipids, genes, and health. Science 312, 698 (2006).
- Miyazaki, M., Bruggink, S. M. and Ntambi, J. M. Identification of mouse palmitoyl-coenzyme A D9-desaturase. J. Lipid Res. 47, 700-704 (2006).
- Sampath, H. and Ntambi, J. M. Stearoyl-coenzyme A desaturase 1, sterol regulatory element binding protein-1c and peroxisome proliferators-activated receptor-a: Independent and interactive roles in the regulation of lipid metabolism. Curr. Opin. Clin. Nutr. Metab. Care 9, 84-88 (2006).
- Harini Sampth and James M. Ntambi (2006) Fate and Intermediary metabolism of Stearic Lipids In Press
Check PubMed for other publications by James M. Ntambi
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