The proposed research is aimed at working out the molecular mechanisms that govern fat-specific gene expression as part of cellular differentiation in the mouse. Much of the proposal concerns stearoyl-CoA desaturase gene 1 (SCD1) regulation in adipose and liver tissue or cell lines. SCD1 is transcriptionally activated during preadipocyte differentiation and is regulated differently by insulin, carbohydrates and fatty acids. The applicant wishes to define the genetic elements associated with the gene as well as several regulatory proteins proposed to mediate the various mechanisms of regulation. He will, in addition, carry out experiments aimed at determining the mechanism through which arachidonic acid inhibits adipocyte differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK042825-06
Application #
2142573
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1990-09-01
Project End
1996-08-31
Budget Start
1995-09-30
Budget End
1996-08-31
Support Year
6
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Sessler, A M; Ntambi, J M (1998) Polyunsaturated fatty acid regulation of gene expression. J Nutr 128:923-6
Singh, M V; Ntambi, J M (1998) Nuclear factor 1 is essential for the expression of stearoyl-CoA desaturase 1 gene during preadipocyte differentiation. Biochim Biophys Acta 1398:148-56
Waters, K M; Miller, C W; Ntambi, J M (1997) Localization of a negative thyroid hormone-response region in hepatic stearoyl-CoA desaturase gene 1. Biochem Biophys Res Commun 233:838-43
Miller, C W; Waters, K M; Ntambi, J M (1997) Regulation of hepatic stearoyl-CoA desaturase gene 1 by vitamin A. Biochem Biophys Res Commun 231:206-10
Waters, K M; Miller, C W; Ntambi, J M (1997) Localization of a polyunsaturated fatty acid response region in stearoyl-CoA desaturase gene 1. Biochim Biophys Acta 1349:33-42
Ntambi, J M; Sessler, A M; Takova, T (1996) A model cell line to study regulation of stearoyl-CoA desaturase gene 1 expression by insulin and polyunsaturated fatty acids. Biochem Biophys Res Commun 220:990-5
Sessler, A M; Kaur, N; Palta, J P et al. (1996) Regulation of stearoyl-CoA desaturase 1 mRNA stability by polyunsaturated fatty acids in 3T3-L1 adipocytes. J Biol Chem 271:29854-8
Ntambi, J M; Takova, T (1996) Role of Ca2+ in the early stages of murine adipocyte differentiation as evidenced by calcium mobilizing agents. Differentiation 60:151-8
Miller, C W; Casimir, D A; Ntambi, J M (1996) The mechanism of inhibition of 3T3-L1 preadipocyte differentiation by prostaglandin F2alpha. Endocrinology 137:5641-50
Waters, K M; Ntambi, J M (1996) Polyunsaturated fatty acids inhibit hepatic stearoyl-CoA desaturase-1 gene in diabetic mice. Lipids 31 Suppl:S33-6

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