Abstract

This Project has been at the center of this Program Project Grant since its inception in 1977. The objective continues to be an understanding of the mechanism by which cells sense cholesterol and adjust its uptake via the LDL receptor pathway and its synthesis via the cholesterol biosynthetic pathway so as to maintain an optimal level of cholesterol in cell membranes. An understanding of this control mechanism may help to explain why ingestion of cholesterol and saturated fatty acids leads to an elevation of LDL in plasma and the consequent atherosclerosis. In recent years, we have learned that an understanding of the SREBP pathway has another implication, equally as important as its implication for cholesterol homeostasis. This implication derives from the evidence that SREBPs regulate the synthesis of unsaturated fatty acids as well as cholesterol. These studies therefore may increase our understanding of the disordered fatty acid synthesis that predisposes to atherosclerosis in states of obesity, insulin resistance, and diabetes mellitus.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL020948-28
Application #
6910656
Study Section
Project Start
2004-07-01
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
28
Fiscal Year
2004
Total Cost
$385,063
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Mitsche, Matthew A; Hobbs, Helen H; Cohen, Jonathan C (2018) Patatin-like phospholipase domain-containing protein 3 promotes transfer of essential fatty acids from triglycerides to phospholipids in hepatic lipid droplets. J Biol Chem 293:6958-6968
Banfi, Serena; Gusarova, Viktoria; Gromada, Jesper et al. (2018) Increased thermogenesis by a noncanonical pathway in ANGPTL3/8-deficient mice. Proc Natl Acad Sci U S A 115:E1249-E1258
Fine, Michael; Schmiege, Philip; Li, Xiaochun (2018) Structural basis for PtdInsP2-mediated human TRPML1 regulation. Nat Commun 9:4192
Linden, Albert G; Li, Shili; Choi, Hwa Y et al. (2018) Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice. J Lipid Res 59:475-487
Johnson, Brittany M; DeBose-Boyd, Russell A (2018) Underlying mechanisms for sterol-induced ubiquitination and ER-associated degradation of HMG CoA reductase. Semin Cell Dev Biol 81:121-128
Qi, Xiaofeng; Schmiege, Philip; Coutavas, Elias et al. (2018) Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex. Science 362:
Engelking, Luke J; Cantoria, Mary Jo; Xu, Yanchao et al. (2018) Developmental and extrahepatic physiological functions of SREBP pathway genes in mice. Semin Cell Dev Biol 81:98-109
Hobbs, Helen H (2018) Science, serendipity, and the single degree. J Clin Invest 128:4218-4223
Muse, Evan D; Yu, Shan; Edillor, Chantle R et al. (2018) Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages. Proc Natl Acad Sci U S A 115:E4680-E4689
DeBose-Boyd, Russell A; Ye, Jin (2018) SREBPs in Lipid Metabolism, Insulin Signaling, and Beyond. Trends Biochem Sci 43:358-368

Showing the most recent 10 out of 766 publications