METTL16-m⁶A-PGC-1α axis contributes to exercise-induced mitochondrial adaptations in skeletal muscle of high-fat diet-fed insulin-resistant mice.

ABSTRACT:

Background

The dynamic change of N6-methyladenosine (m⁶A) modification on substrate RNA molecules plays a critical role in different biological processes and disease pathogenesis. Although the beneficial effects of exercise training (ET) on skeletal muscle insulin resistance (IR) are well-established, the contribution of RNA m⁶A modification in ET-related adaptations in high-fat diet (HFD)-induced IR remains unclear.

Results

In this study, we show that exercise stimulation triggers a dynamic shift in skeletal muscle m⁶A modification levels during HFD consumption. As a key m⁶A methyltransferase, METTL16 was downregulated in HFD-fed mice and upregulated by ET at both the mRNA and protein levels. In vitro, METTL16 knockdown disrupted

SUBMITTER: Chen C 

PROVIDER: S-EPMC12911173 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature