BioProject

PGC1beta is a transcriptional coactivator that potently stimulates mitochondrial biogenesis and respiration of cells. More...

PGC1beta is a transcriptional coactivator that potently stimulates mitochondrial biogenesis and respiration of cells. Here, we have generated mice lacking exons 3 to 4 of the Pgc1beta gene (PGC1beta E3,4-/E3,4- mice). These mice express a mutant protein that has reduced coactivation activity on a subset of transcription factors, including ERRalpha, a major target of PGC1beta in the induction of mitochondrial gene expression. The mutant mice have reduced expression of OXPHOS genes and mitochondrial dysfunction in liver and skeletal muscle as well as elevated liver triglycerides. Euglycemic-hyperinsulinemic clamp and insulin signaling studies show that PGC1beta mutant mice have normal skeletal muscle response to insulin, but have hepatic insulin resistance. These results demonstrate that PGC1beta is required for normal expression of OXPHOS genes and mitochondrial function in liver and skeletal muscle. Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver. Keywords: Liver and quadricpes muscle gene expression, WT vs. PGC1beta mutant Overall design: Gene expression levels in liver tissue and quadriceps muscle were compared between WT/Control and PGC1beta mutant tissue. Total RNA was extracted from liver and skeletal muscle using RNAeasy kit (Qiagen, Valencia, CA), according to the manufacturer’s instructions. Synthesis of cRNA, hybridization and scanning of the Affymetrix Murine 430 2.0 chip was performed by Dana Farber Cancer Institute Microarray Core Facility. The microarray data was analyzed by Clustering Analysis using the d-Chip software (Li and Wong, 2001). Less...