Muscle-Specific Myosin Heavy Chain Shifts in Response to a Long-Term High Fat/High Sugar Diet and Resveratrol Treatment in Nonhuman Primates.

Jon-Philippe K Hyatt,Rafael De Cabo,Allison E Hall,Ashley M Huber,Julie A Mattison,Robert J Talmadge,Jeannine R Larocque,Lisa Nguyen,Jessica C Kocan

doi:10.3389/fphys.2016.00077

Abstract

Shifts in myosin heavy chain (MHC) expression within skeletal muscle can be induced by a host of stimuli including, but not limited to, physical activity, alterations in neural activity, aging, and diet or obesity. Here, we hypothesized that both age and a long-term (2 year) high fat/high sugar diet (HFS) would induce a slow to fast MHC shift within the plantaris, soleus, and extensor digitorum longus (EDL) muscles from rhesus monkeys. Furthermore, we tested whether supplementation with resveratrol, a naturally occurring compound that has been attributed with augmenting aerobic potential through mitochondrial proliferation, would counteract any diet-induced MHC changes by promoting a fast to slow isoform switch. In general, we found that MHC isoforms were not altered by aging during mid-life. The HFS diet had the largest impact within the soleus muscle where the greatest slow to fast isoform shifts were observed in both mRNA and protein indicators. As expected, long-term resveratrol treatment counteracted, or blunted, these diet-induced shifts within the soleus muscle. The plantaris muscle also demonstrated a fast-to-slow phenotypic response to resveratrol treatment. In conclusion, diet or resveratrol treatment impacts skeletal muscle phenotype in a muscle-specific manner and resveratrol supplementation may be one approach for promoting the fatigue-resistant MHC (type I) isoform especially if its expression is blunted as a result of a long-term high fat/sugar diet.

Highlights

Skeletal muscle phenotype is determined, in part, by the type of myosin heavy chain (MHC) protein expressed throughout the tissue
After 2 years on the high fat/high sugar diet, the average body mass for both HFS and HFSR monkeys was 32 and 25% greater than Con-O animals, respectively (p < 0.05)
We found that the soleus is the most sensitive to a high fat/sugar diet, which manifested as a higher relative proportion of type II a/x MHC

Summary

Introduction

Skeletal muscle phenotype is determined, in part, by the type of myosin heavy chain (MHC) protein expressed throughout the tissue. Relative to fast muscles (with a preponderance of type II fibers), MHC Isoform Shifts in Nonhuman Primates slow (type I) muscles are high in capillary density and mitochondrial volume, contain a greater proportion of aerobic enzymes, and are generally fatigue resistant. A high fat diet has been shown to reduce the percentage of fibers expressing type I MHC in rodent and human muscles, suggesting a reduction in overall oxidative capacity, insulin sensitivity, and glucose tolerance (Lillioja et al, 1987; Abou Mrad et al, 1992; Hickey et al, 1995; Kriketos et al, 1996)

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