Abstract

The PI has a long-standing interest in fatty acid binding proteins. The present proposal hinges on studies of two such proteins, aP2 and KLBP. The hypothesis of this proposal is that aP2, but not KLBP, stimulates gene transcription by delivering lipid ligands to the lipid activated transcription factor PPAR gamma 2. Since aP2 knock-out mice develop obesity only on a high fat diet, and such obesity is uncoupled from insulin resistance and TNF alpha production, the PI hypothesizes that aP2 affects the development of obesity by trafficking hydrophobic ligand to nuclear transcription factors, thereby regulating the expression of genes whose products are involved in the development of insulin resistance and NIDDM. The PI proposes the following set of experiments to test the hypothesis: A. To express wild-type and lipid binding proteins in aP2 and KLBP null mice, and to assess the expression of TNF alpha and the development of insulin resistance in these mice under different dietary conditions; B. To characterize the interactions between aP2 and PPAR gamma 1 and 2 in response to thiazolidinediones and polyunsaturated fatty acids; and C to examine lipid trafficking in adipocytes derived from KLBP and ap2 null mice using retroviral expression techniques.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK053189-03
Application #
6178122
Study Section
Metabolism Study Section (MET)
Program Officer
Haft, Carol R
Project Start
1998-08-12
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2002-07-31
Support Year
3
Fiscal Year
2000
Total Cost
$197,730
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Jahansouz, C; Xu, H; Hertzel, A V et al. (2018) Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery. Int J Obes (Lond) 42:139-146
Duffy, Cayla M; Xu, Hongliang; Nixon, Joshua P et al. (2017) Identification of a fatty acid binding protein4-UCP2 axis regulating microglial mediated neuroinflammation. Mol Cell Neurosci 80:52-57
Hertzel, Ann V; Xu, Hongliang; Downey, Michael et al. (2017) Fatty acid binding protein 4/aP2-dependent BLT1R expression and signaling. J Lipid Res 58:1354-1361
Steen, Kaylee A; Xu, Hongliang; Bernlohr, David A (2017) FABP4/aP2 Regulates Macrophage Redox Signaling and Inflammasome Activation via Control of UCP2. Mol Cell Biol 37:
Xu, Hongliang; Hertzel, Ann V; Steen, Kaylee A et al. (2016) Loss of Fatty Acid Binding Protein 4/aP2 Reduces Macrophage Inflammation Through Activation of SIRT3. Mol Endocrinol 30:325-34
Hotamisligil, Gökhan S; Bernlohr, David A (2015) Metabolic functions of FABPs--mechanisms and therapeutic implications. Nat Rev Endocrinol 11:592-605
Jahansouz, Cyrus; Serrot, Federico J; Frohnert, Brigitte I et al. (2015) Roux-en-Y Gastric Bypass Acutely Decreases Protein Carbonylation and Increases Expression of Mitochondrial Biogenesis Genes in Subcutaneous Adipose Tissue. Obes Surg 25:2376-85
Ali, Asem H; Mundi, Manpreet; Koutsari, Christina et al. (2015) Adipose Tissue Free Fatty Acid Storage In Vivo: Effects of Insulin Versus Niacin as a Control for Suppression of Lipolysis. Diabetes 64:2828-35
Xu, Hongliang; Hertzel, Ann V; Steen, Kaylee A et al. (2015) Uncoupling lipid metabolism from inflammation through fatty acid binding protein-dependent expression of UCP2. Mol Cell Biol 35:1055-65
Mandrup, Susanne; MacDougald, Ormond A; Moss, Joel et al. (2014) In memoriam: M. Daniel Lane, 1930-2014. Trends Endocrinol Metab 25:437-9

Showing the most recent 10 out of 48 publications