Muscle-specific differences in the response of mitochondrial proteins to {beta}-GPA feeding: an evaluation of potential mechanisms

1 Alberta Diabetes Institute, University of Alberta, Edmonton; and 2 Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada Submitted 13 November 2008 ; accepted in final form 22 March 2009 β-Guanadinopropionic acid (β-GPA) feeding leads to reductions in skeletal muscle phosphagen concentrations and has been used as a tool with which to study the effects of energy charge on skeletal muscle metabolism. Supplementing standard rodent diets with β-GPA leads to increases in mitochondrial enzyme content in fast but not slow-twitch muscles from male rats. Given this apparent discrepancy between muscle types we used β-GPA feeding as a model to study signaling pathways involved in mitochondrial biogenesis. We hypothesized that β-GPA feeding would result in a preferential activation of p38 MAPK and AMPK signaling and reductions in RIP140 protein content in triceps but not soleus muscle. Despite similar reductions in high-energy phosphate concentrations, 6 wk of β-GPA feeding led to increases in mitochondrial proteins in triceps but not soleus muscles. Differences in the response of mitochondrial proteins to β-GPA feeding did not seem to be related to a differential activation of p38 MAPK and AMPK signaling pathways or discrepancies in the induction of PPAR coactivator (PGC)-1 and -1β. The protein content and expression of the nuclear corepressor RIP140 was reduced in triceps but not soleus muscle. Collectively our results indicate that chronic reductions in high-energy phosphates lead to the activation of p38 MAPK and AMPK signaling and increases in the expression of PGC-1 and -1β in both soleus and triceps muscles. The lack of an effect of β-GPA feeding on mitochondrial proteins in the soleus muscles could be related to a fiber type-specific effect of β-GPA on RIP140 protein content. β-guanadinopropionic acid; peroxisome proliferator-activated receptor- coactivator-1 ; skeletal muscle; rat; kinase; RIP140 Address for reprint requests and other correspondence: D. C. Wright, Alberta Diabetes Institute, 4126C HRIF East, Univ. of Alberta, Edmonton, Alberta, Canada T6G 2E1 (E-mail: dcw3{at}ualberta.ca )