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.

A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats

“…Notably, as previous studies have indicated that diet-induced obesity disrupts muscle repair processes19, the fibrosis observed in this study may be interpreted as HFS-induced muscle damage or disrupted repair. Here, the increased fibrosis observed by 3-days on the HFS diet is among the earliest reports of compromised muscle integrity with short-term metabolic challenge.…”

Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice

“…De-regulated niche signals eventually lead to stem cell dysfunction and inefficient tissue repair. Of note, a number of multisystemic conditions—such as aging, diabetes, obesity and cancer cachexia—are also accompanied by a loss of MuSC function and consequently by a decline of the regenerative capacity of skeletal muscle tissue 9–12 . In the elderly, this problem is also paralleled by a loss of MuSC numbers, resulting in dramatically delayed or incomplete healing of muscle following injury or surgery 13–15 .…”

Plane of nutrition affects growth rate, organ size and skeletal muscle satellite cell activity in newborn calves

“…The state of quiescence is tightly regulated by HGF; the growth factor is required for activation or exit from G 0 (Allen et al., ; Sheehan et al., ) and elevated HGF concentrations drive the satellite cell into quiescence (Yamada et al., ). Nutritional excess leading to obesity blunts the satellite cell response to HGF and disrupts muscle regeneration (D'Souza et al., ). In support of our results, caloric restriction in mice increases the numbers of rapidly dividing satellite cells in vitro (Cerletti et al., ).…”