PGC-1α: a key regulator of energy metabolism

Abstract

Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is a member of a family of transcription coactivators that plays a central role in the regulation of cellular energy metabolism. It is strongly induced by cold exposure, linking this environmental stimulus to adaptive thermogenesis. PGC-1alpha stimulates mitochondrial biogenesis and promotes the remodeling of muscle tissue to a fiber-type composition that is metabolically more oxidative and less glycolytic in nature, and it participates in the regulation of both carbohydrate and lipid metabolism. It is highly likely that PGC-1alpha is intimately involved in disorders such as obesity, diabetes, and cardiomyopathy. In particular, its regulatory function in lipid metabolism makes it an inviting target for pharmacological intervention in the treatment of obesity and Type 2 diabetes.

Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction

“…HK‐II and PFK are the main rate‐controlling enzymes of glycolytic flux while PDH activity, which catalyzes the conversion of pyruvate to acetyl‐CoA, modulates mitochondrial glucose and fatty acid fluxes. Mitochondrial fatty acid (FA) β‐oxidation is a metabolic feature promoted by CR and exercise that is controlled by PGC‐1α, a member of a family of transcriptional coactivators, and the protein deacetylase SIRT3 (Hirschey et al., 2010; Liang & Ward, 2006). Western blot analysis showed significant accumulation of PGC‐1α and SIRT3 in muscle of RedTg mice compared to Wt controls (Figure 2c,d).…”

Glucose levels and genetic variants across transcriptional pathways: interaction effects with BMI

“…PPARGC1A is a transcriptional co-activator that interacts with a broad range of transcription factors involved in a wide variety of biological processes, including glucose metabolism in the liver and muscle, mitochondrial biogenesis, lipid oxidation, and adipocyte differentiation. 22 One of the transcription factors regulated by PPARGC1A is PPARG. In line with the interaction effect of PPARGC1A with BMI in our study, Wei et al 7 found a significant interaction effect between two SNPs in the PPARG gene (rs4135304; rs4135247) and BMI on fasting plasma glucose levels in African Americans.…”

“…In liver, PPARGC1A down-regulation decreases gluconeogenesis, 22 which has a blood glucose lowering effect. In contrast, in vitro studies suggest that down-regulation of PPARGC1A in muscle increases insulin resistance by down-regulating GLUT4 transporters 22 and by stimulating muscle lipid accumulation. 33 This, in turn, increases blood glucose levels.…”

Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene (PGC1A) during weight loss is related to insulin sensitivity but not to energy expenditure

“…PGC1A and its target mitofusin-2 (MFN2) are both involved in mitochondrial biogenesis and in the maintenance of the mitochondrial network [6][7][8]. Moreover, MFN2 augments mitochondrial oxidative capacity for both glucose and lipids [9] and PGC1A increases expression of the insulinsensitive glucose transporter 4 [10].…”