High fat feeding does not impair muscle growth in MuRF1 KO mice (1163.17)

Abstract

Obesity is rapidly becoming a global epidemic and is associated with a number of chronic diseases including type II diabetes, metabolic syndrome, and cardiovascular disease. In skeletal muscle, chronic exposure to high levels of fatty acids can decrease oxidative capacity and increase endoplasmic reticulum (ER) stress, both of which could contribute to an attenuation of load‐induced growth. MuRF1 is an E3 ubiquitin ligase that is associated with muscle atrophy. MuRF1 null (KO) mice have been shown to spare muscle mass under atrophy conditions, and more recently we have shown that MuRF1 KO mice exhibit a superior ability to hypertrophy with age, suggesting that MuRF1 plays a role in the acquisition of anabolic resistance. Thus, the aim of this study was to determine if MuRF1 KO mice develop anabolic resistance in response to a high fat diet. Beginning at six weeks of age, male WT and MuRF1 KO mice were divided into two diet groups: mice fed a high fat diet (45% fat, HFD) and mice fed a normal chow diet (10% fat, LFD). At 20 weeks, a subset of mice from each diet group was subjected to bilateral functional overload (FO) for 14 days. WT HFD mice had significantly less hypertrophy than WT LFD mice (31% vs. 76% growth), while the MuRF1 KO HFD mice showed no growth impairment (76% growth). Expression of ER stress markers were highest in the WT HFD mice. Interestingly, MuRF1 KO mice on a HFD appeared to accumulate less intramuscular fat compared to the HFD WT mice. These results suggest that the accumulation of intramuscular fat and an increase in ER stress may be responsible for the development of anabolic resistance in mice fed a HFD.