The long term objectives of this research proposal involve understanding the phenomenon of molecular compensation with respect to the fatty acid binding protein (FABP), keratinocyte lipid binding protein (KLBP). This gene is normally expressed in lens epithelial cells, and is found in low levels in several other tissues, but was first discovered as an upregulated message in skin carcinomas and papillomas. Additionally, KLBP has been found to be highly upregulated in adipose from mice containing a knockout of the adipocyte lipid binding protein (ALBP) gene. These cells have some mechanism to sense the change resulting from the lack of KLBP and compensate by inducing KLBP expression. This proposal focuses on understanding the regulation of KLBP in this latter condition. The first part involves cloning the KLBP gene in order to allow the study of the DNA sequences necessary for the upregulation of KLBP in primary adipocytes from mice lacking ALBP. The transcription factor(s) necessary for the upregulation of KLBP will be identified. It is hypothesized that the factors involved include the peroxisome proliferator activated receptors (PPAR), members of the steroid hormone supergene family. The results of the experiments will provide an understanding of the unique phenomenon of molecular compensation, as well as giving insights into the role of FABP in cancer cells, and the involvement of fatty acids in regulating gene expression through PPARs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK009599-03
Application #
2900100
Study Section
Special Emphasis Panel (ZRG2-MET (01))
Program Officer
Hyde, James F
Project Start
1999-04-01
Project End
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
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
Michels, Aaron W (2013) Targeting the trimolecular complex. Clin Immunol 149:339-44
Michels, Aaron W (2013) Targeting the trimolecular complex: the pathway towards type 1 diabetes prevention. Diabetes Technol Ther 15 Suppl 2:S2-8-S2-12
Hertzel, A V; Sanders, M A; Bernlohr, D A (2000) Adenovirus-mediated gene transfer in primary murine adipocytes. J Lipid Res 41:1082-6
Hertzel, A V; Bernlohr, D A (2000) The mammalian fatty acid-binding protein multigene family: molecular and genetic insights into function. Trends Endocrinol Metab 11:175-80
Hertzel, A V; Bernlohr, D A (1998) Regulation of adipocyte gene expression by polyunsaturated fatty acids. Mol Cell Biochem 188:33-9
Hertzel, A V; Bernlohr, D A (1998) Cloning and chromosomal location of the murine keratinocyte lipid-binding protein gene. Gene 221:235-43