title: Muscle-specific differences in the response of mitochondrial proteins to beta-GPA feeding: an evaluation of potential mechanisms.
abstract: Beta-Guanadinopropionic acid (beta-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 beta-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 beta-GPA feeding as a model to study signaling pathways involved in mitochondrial biogenesis. We hypothesized that beta-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 beta-GPA feeding led to increases in mitochondrial proteins in triceps but not soleus muscles. Differences in the response of mitochondrial proteins to beta-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 PPARgamma coactivator (PGC)-1alpha and -1beta. 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-1alpha and -1beta in both soleus and triceps muscles. The lack of an effect of beta-GPA feeding on mitochondrial proteins in the soleus muscles could be related to a fiber type-specific effect of beta-GPA on RIP140 protein content.
authors.affiliation: Alberta Diabetes Institute, 4126C HRIF East, Univ. of Alberta, Edmonton, Alberta, Canada T6G 2E1.
authors.forename: Deon B
authors.initials: DB
authors.lastname: Williams
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Sutherland
authors.forename: Marc R
authors.initials: MR
authors.lastname: Bomhof
authors.forename: Susan A U
authors.initials: SA
authors.lastname: Basaraba
authors.forename: A Brianne
authors.initials: AB
authors.lastname: Thrush
authors.forename: David J
authors.initials: DJ
authors.lastname: Dyck
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Field
authors.forename: David C
authors.initials: DC
authors.lastname: Wright