Adaptive gene expression of alternative splicing variants of PGC-1α regulates whole-body energy metabolism.

ABSTRACT: The transcriptional coactivator PGC-1α has been implicated in the regulation of multiple metabolic processes. However, the previously reported metabolic phenotypes of mice deficient in PGC-1α have been inconsistent. PGC-1α exists as multiple isoforms, including variants transcribed from an alternative first exon. We show here that alternative PGC-1α variants are the main entity that increases PGC-1α during exercise. These variants, unlike the canonical isoform of PGC-1α, are robustly upregulated in human skeletal muscle after exercise. Furthermore, the extent of this upregulation correlates with oxygen consumption. Mice lacking these variants manifest impaired energy expenditure during exercise, leading to the development of obesity and hyperinsulinemia. The alternative variants are also u

SUBMITTER: Nomura K 

PROVIDER: S-EPMC11254180 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature