Dietary medium-chain triglycerides upregulate metabolic gene expression in the gastrocnemius and downregulate expression of muscle-degradation gene in the soleus in aged bromodomain-containing 4+/- heterozygous mice

Abstract

Purpose

Bromodomain containing 4 (BRD4) positively regulates metabolic gene expression, and Brd4^+/- heterozygous mice exhibit leanness and malnutrition-like features. We evaluated gene expression changes, particularly of metabolism and muscle synthesis/degradation, in the skeletal muscles of aged Brd4^+/- mice fed a high medium-chain triglyceride (MCT) diet.

Methods

Each organ weight of C57BL/6J male wild-type and Brd4^+/-/C57BL/6J mice were assessed at approximately 100 weeks old. Male Brd4^+/-/C57BL/6J mice (aged 54–84 weeks) were fed a control or MCT diet for approximately 5 months and mRNA expression changes in the gastrocnemius and soleus were quantified using mRNA microarray analysis and qRT-PCR.

Results

Gastrocnemius and soleus weights decreased markedly in aged Brd4^+/-, compared to wild-type mice; MCT-fed Brd4^+/- mice had decreased mesenteric adipose tissue weight but no decrease in gastrocnemius and soleus weights. Metabolic gene expression was downregulated more in the gastrocnemius than in the soleus. Metabolic genes, including glycolytic and citric acid cycle, and Myh3, mediating regeneration of the skeletal muscle, in gastrocnemius, were upregulated in MCT-diet-fed Brd4^+/-, whereas Murf1, which promotes degradation, was downregulated in soleus.

Conclusions

An MCT-rich diet altered mRNA expression of metabolic and muscle-regeneration and -degradation genes in the gastrocnemius and soleus of Brd4^+/- mice.