PPARβ/δ is not required by PGC‐1α to enhance skeletal muscle oxidative metabolism (1164.3)

Abstract

Impaired skeletal muscle metabolism is a hallmark of numerous, chronic metabolic diseases. Exercise training efficiently improves skeletal muscle metabolic fitness, increases mitochondrial biogenesis and exerts beneficial therapeutic effects. Aberrant expression of metabolic‐related genes in skeletal muscle is thought to contribute to the development and progression of such pathologies. The peroxisome proliferator‐activated receptor γ (PPARγ) coactivator‐1α (PGC‐1α) and the nuclear receptor PPARβ/δ have both been independently shown to increase skeletal muscle oxidative capacity and exercise performance. Therefore, current understanding is that the PGC‐1α‐PPARβ/δ axis plays a pivotal role in the regulation of skeletal muscle metabolism. However, the interplay and hierarchical regulation of these two proteins remains unclear, with limited research conducted in vivo. In the present study, we demonstrate that the disruption of the PGC‐1α‐PPARβ/δ axis in mouse skeletal muscle does not affect body composition, whole body metabolism and glucose homeostasis under basal conditions. Importantly, PPARβ/δ seems dispensable for most of the effects of PGC‐1α on VO2 and lactate metabolism during exercise as well as the enhancement of skeletal muscle oxidative metabolism. Therefore, these results indicate that PPARβ/δ is not an essential partner of PGC‐1α in the control of skeletal muscle remodeling.Grant Funding Source: Supported by the Swiss National Science Foundation