# Skeletal muscle‐specific PGC‐1α‐b overexpression prevents eccentric contraction‐induced muscle injury through an utrophin‐independent pathway in mice

## TL;DR

A protein called PGC-1α-b helps protect muscle fibers from injury caused by certain types of exercise in mice, even without another protein called utrophin.

## Contribution

PGC-1α-b overexpression protects glycolytic muscle fibers from ECC-induced injury independently of utrophin.

## Key findings

- PGC-1α-b transgenic mice showed rapid recovery of muscle torque after injury.
- These mice had minimal membrane damage and calpain-1 activation.
- PGC-1α-b preserved excitation-contraction coupling proteins and increased mitochondrial markers.

## Abstract

Slower oxidative fibers are more resistant to eccentric contraction (ECC)‐induced muscle damage than fast‐twitch glycolytic fibers, but the mechanisms remain unclear. This study investigated the roles of the exercise‐inducible PGC‐1α isoform PGC‐1α‐b and utrophin in protecting against ECC‐induced damage. ECCs were induced by supramaximal electrical stimulation of the left triceps surae in C57BL/6N wild‐type (WT), PGC‐1α‐b transgenic (Tg), utrophin knockout (Utrn KO), and PGC‐1α‐b Tg/Utrn KO mice. Although the proportion of fast‐type myosin heavy chain (MyHC) IIb in the gastrocnemius muscle was modestly lower in PGC‐1α‐b Tg and PGC‐1α‐b Tg/Utrn KO mice than in WT and Utrn KO mice, MyHC IIb remained the predominant isoform. At 3 days post injury (dpi), WT and Utrn KO mice exhibited reduced maximum isometric torque (MIT), Evans blue dye (EBD) staining in MyHC IIb‐positive fibers, and calpain‐1 activation. In contrast, PGC‐1α‐b Tg and PGC‐1α‐b Tg/Utrn KO mice showed substantial MIT recovery at 1 dpi and minimal EBD uptake and calpain‐1 activation at 3 dpi. PGC‐1α‐b Tg muscles also preserved excitation‐contraction coupling proteins and displayed increased mitochondrial markers and integrin α7B expression. Together, our findings suggest that PGC‐1α‐b confers resistance to ECC‐induced muscle damage through a Utrn‐independent mechanism.

PGC‐1α‑b overexpression protects glycolytic muscle fibers from eccentric contraction–induced injury. Eccentric contractions caused marked membrane damage and loss of maximal isometric torque in wild‐type and utrophin‐deficient mice, particularly within MyHC IIb–dominant fibers. In contrast, PGC‑1α‑b transgenic mice, regardless of utrophin expression, showed rapid torque recovery and minimal Evans blue dye uptake. These findings identify PGC‑1α‑b as a potent, utrophin‐independent protector against ECC‑induced muscle damage.