title: Diet-induced obesity impairs muscle satellite cell activation and muscle repair through alterations in hepatocyte growth factor signaling.
abstract: A healthy skeletal muscle mass is essential in attenuating the complications of obesity. Importantly, healthy muscle function is maintained through adequate repair following overuse and injury. The purpose of this study was to investigate the impact of diet-induced obesity (DIO) on skeletal muscle repair and the functionality of the muscle satellite cell (SC) population. Male C57BL/6J mice were fed a standard chow or high-fat diet (60% kcal fat; DIO) for 8 weeks. Muscles from DIO mice subjected to cardiotoxin injury displayed attenuated muscle regeneration, as indicated by prolonged necrosis, delayed expression of MyoD and Myogenin, elevated collagen content, and persistent embryonic myosin heavy chain expression. While no significant differences in SC content were observed, SCs from DIO muscles did not activate normally nor did they respond to exogenous hepatocyte growth factor (HGF) despite similar receptor (cMet) density. Furthermore, HGF release from crushed muscle was significantly less than that from muscles of chow fed mice. This study demonstrates that deficits in muscle repair are present in DIO, and the impairments in the functionality of the muscle SC population as a result of altered HGF/c-met signaling are contributors to the delayed regeneration.
authors: Departments of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Donna M
authors: DM
authors: D'Souza
authors: Departments of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Karin E
authors: KE
authors: Trajcevski
authors: Departments of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Dhuha
authors: D
authors: Al-Sajee
authors: Departments of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: David C
authors: DC
authors: Wang
authors: Departments of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Melissa
authors: M
authors: Thomas
authors: Department of Biological Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Judy E
authors: JE
authors: Anderson
authors: Departments of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada hawke@mcmaster.ca.
authors: Thomas J
authors: TJ
authors: Hawke
keywords: Diet‐induced obesity; growth factors; muscle repair; satellite cell