Brian N. Finck, Ph.D.

Washington University
School of Medicine

Dept. of Medicine
Div. of Geriatrics & Nutritional Science
Box 8031
660 S. Euclid Ave.
St. Louis, MO 63110

tel: (314) 362-8963
fax: (314) 362-8230
email: bfinck@im.wustl.edu
web: Personal Weblink

 

 

RESEARCH INTEREST

We are interested in the effects of a protein called lipin 1 on liver metabolism in health and disease. Lipin is an intracellular protein that plays multiple roles in regulating energy metabolism. Recent work suggests that lipin acts in the cytosol of cells as an enzyme involved in triglyceride synthesis. We have recently shown that lipin also acts in the nucleus to regulate the expression of many genes governing energy metabolism. Our basic science program is aimed at understanding the molecular mechanisms whereby lipin impacts energy metabolism by using strategies to genetically activate, deactivate, or selectively mutate lipin activity in mice and cultured cells. We use a broad array of techniques including gene expression profiling, sophisticated molecular biological techniques, and metabolic quantification. Through collaborations with other investigators conducting clinical studies, we are also quantifying the expression of lipin and its target genes involved in energy metabolism in normal and diseased liver. Ongoing projects involve studies with (1) obese human subjects undergoing gastric bypass surgery and (2) patients with non-alcoholic steatohepatitis compared to patients with other chronic non-viral liver diseases or normal controls.

SELECTED PUBLICATIONS

1) Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, Han X, Gross RW, Kozak R, Lopaschuk GD, and Kelly DP. 2002. The cardiac phenotype induced by PPARα overexpression mimics that caused by diabetes mellitus. J. Clin. Invest. 109:121-130.

2) Finck BN, Han X, Courtois M, Aimond F, Nerbonne JM, Kovacs A, Gross RW, and Kelly DP. 2003. A critical role for PPARα-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation by dietary fat content. Proc. Natl. Acad. Sci. USA 100:1226-1231.

3) Bernal-Mizrachi C, Weng S, Feng C, Finck BN, Knutsen RH, Leone TC, Coleman T, Mecham RP, Kelly DP, and Semenkovich CF. 2003. Glucocorticoid induction of hypertension and diabetes is PPARα-dependent in mice. Nat. Med. 9:1069-1075.

4) Finck BN, Bernal-Mizrachi C, Han DH, Coleman T, Sambandam N, LaRiviere LL, Holloszy JO, Semenkovich CF, and Kelly DP. 2005. A potential link between muscle peroxisome proliferator-activated receptor α signaling and obesity-induced insulin resistance. Cell Metab. 1:133-144.

5) Burgess SC, Leone TC, Wende AR, Croce MA, Chen Z, Sherry AD, Malloy CR, and Finck BN. 2006. Diminished hepatic gluconeogenesis via defects in tricarboxylic acid cycle flux in peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-deficient mice. J. Biol. Chem. 281: 19000-19008.

6) Finck BN and Kelly DP. 2006. PGC-1 Coactivators: Inducible Regulators of Energy Metabolism in Health and Disease. J. Clin. Invest. 116:615-622. (Review)

7) Finck BN, Gropler MC, Chen Z, Leone TC, Croce MA, Harris TE, Lawrence JC, and Kelly DP. 2006. Lipin 1 is an inducible amplifier of the hepatic PGC-1α / PPARα regulatory pathway. Cell Metab. 4: 199-210.