Biochemistry, Molecular Biology and Biophysics

David A. Bernlohr

Distinguished McKnight
Professor and Head

Research Interests

Metabolic control and regulation in adipocytes, obesity/insulin action, lipid metabolism, protein-lipid association, lipid oxidation, proteomics.

Research in the Bernlohr laboratory focuses on the integration of metabolic regulation, lipid metabolism, gene expression and systems biology towards an understanding of obesity-linked diseases such as Type 2 diabetes, cardiovascular disease and hypertension.

The work focuses on three major projects:

The role of fatty acid binding proteins (FABP) as lipid sensors and regulators of metabolism.

In this project we use a combination of animal (knockout and transgenic) and cell culture (3T3-L1 adipocytes) models to evaluate protein-protein interaction between the intracellular FABPs and intracellular targets linked to gene expression and inflammatory diseases.

Smith, A.J., Thompson, B.R., Sanders, M.A., and Bernlohr, D.A. (2007) Interaction of the Adipocyte Fatty Acid Binding Protein with the Hormone Sensitive Lipase: Regulation by Fatty Acids and Phosphorylation. J. Biol. Chem., 282; 32424-32432

Zhang, J., Wright, W., Bernlohr, D.A., Cushman, S.W., and Chen, X (2007) Alteration in the Classic Pathway of Complement in Adipose Tissue of Obesity and Insulin Resistance. Am J. Physiol Endocrinol Metab 292; E1433-E1440

Zhang, J., Wu, Y., Zhang, Y., LeRoith, D., Bernlohr,D.A., and Chen, X. (2007) The Role of Lipocalin 2 in the Regulation of Inflammation and Insulin Action in Adipocytes and Macrophages. Molecular Endocrinology 22; 1416-1422

Hertzel, A.V., Smith, L.S., Berg, A.Hl, Cline, G.V., Shulman, G.I., Scherer, P., and Bernlohr, D.A. (2006) Lipid Metabolism and Adipokine Levels in Fatty Acid Binding Protein Null and Transgenic Mice. Am. J. Physiol. Endo. Metab. 290: E814 - E823

The mechanisms by which oxidative stress leads to the covalent modification of proteins by lipids and how such modification leads to insulin resistance.

This project links proteomics and metabolomics to modification of critical target proteins implicated in the development of Type 2 diabetes.

Grimsrud, P.A., Picklo, M.J., Griffin, T.J., and Bernlohr, D.A. (2007) Carbonylation of Adipose Proteins in Obesity and Insulin Resistance: Identification of Adipocyte Fatty Acid-binding Protein as a Cellular Target of 4-Hydroxynonenal. Mol Cell Proteomics, 6: 624-637

Grimsrud, P.A., Xie, H., Griffin, T.J., and Bernlohr,D.A. (2008) Oxidative Stress and Covalent Modification of Protein with Bioactive Aldehydes. J. Biol. Chem., 283; 21837-21841

The control of lipid flux into and out of cells via fatty acid CoA ligases that function as lipid transporters.

Using a combination of in-vitro and in-situ studies, coupled with RNAi-based knockdown strategies we have demonstrated which cellular proteins facilitate fatty acid flux into and out of adipocytes and how hormones such as insulin and glucagon can regulate such flux.

Lobo, S., Wiczer, B.M., Smith, A.J., and Bernlohr, D.A. (2007) Fatty Acid Metabolism in Adipocytes: functional Analysis of Fatty Acid Transport Proteins 1 and 4. J. Lipid Res. 48:609-20

Lobo, S. and Bernlohr, D.A. (2007) Lipid Trafficking in the Adipocyte. Novartis Symposium on Fatty Acids and Lipotoxicity in Obesity and Diabetes Vol 286; 113-126