Work

Glucose Directly Links to Lipid Metabolism through High Affinity Interaction with Peroxisome Proliferator-activated Receptor α

Year: 2007

Type: article

Abstract: The pathophysiology of diabetes is characterized not only by elevated glucose but also elevated long chain fatty acid levels. We show for the first time that the peroxisome proliferator-activated receptor-alpha (PPARalpha) binds glucose and glucose metabolites with high affinity, resulting in significantly altered PPARalpha secondary structure. Glucose decreased PPARalpha interaction with fatty acid metabolites and steroid receptor coactivator-1 while increasing PPARalpha interaction with DNA. Concomitantly, glucose increased PPARalpha interaction with steroid receptor coactivator-1, DNA binding, and transactivation of beta-oxidation pathways in the presence of activating ligands. Heterodimerization of PPARalpha to the retinoid X receptor-alpha resulted in even larger increases in transactivation with the addition of glucose. These data suggest that PPARalpha is responsible for maintaining energy homeostasis through a concentration-dependent regulation of both lipids and sugars and that hyperglycemic injury mediated by PPARalpha occurs not only indirectly through elevated long chain fatty acid levels but also through direct action of glucose on PPARalpha.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m705138200

Authors: Heather A. Hostetler, Huan Huang, Ann B. Kier, Friedhelm Schroeder

Institution: Texas A&M University

Language: English

Topic: Peroxisome Proliferator-Activated Receptors

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430