Reduced PGC-1β protein expression may underlie corticosterone inhibition of mitochondrial biogenesis and oxidative phosphorylation in chicken muscles

Abstract

To uncover the molecular mechanism underlying glucocorticoid-induced loss of mitochondrial integrity in skeletal muscles, studies were performed to investigate whether the peroxisome proliferator-activated receptor γ coactivator 1 (<b>PGC-1</b>)-mediated pathway was involved in this process. In an <i>in vivo</i> trial, 3 groups of 30-d-old Arbor Acres male broilers were randomly subjected to one of the following treatments for 7 days: corticosterone (<b>CORT</b>, 30 mg/kg diet), control (blank), and pair-feeding (restricted to the same feed intake as for the CORT treatment), each with 6 replicates of 15 birds. Mitochondrial abundance, morphology, and function were determined in the <i>pectoralis major</i> and <i>biceps femoris</i> muscles. In an <i>in vitro</i> trial, a primary culture of embryonic chick myotubes was incubated with a serum-free medium for 24 h in the presence or absence of CORT (0, 200, and 1,000 nM). Results showed that CORT destroyed mitochondrial ultrastructure (<i>p</i> < 0.01), and decreased the enzymatic activity and protein expression of respiratory chain complexes (<i>p</i> < 0.05), leading to an inferior coupling efficiency (<i>p</i> < 0.05). As reflected by a decline in mitochondrial density (<i>p</i> < 0.01) and mitochondrial DNA copy number (<i>p</i> < 0.05), CORT reduced mitochondrial contents. Among all three PGC-1 family members, only PGC-1β was down-regulated by CORT at the protein level (<i>p</i> < 0.05). Some aspects of these responses were tissue-specific and seemed to result from the depressed feed intake. Overall, CORT may impair mitochondrial biogenesis and oxidative phosphorylation in a PGC-1β-dependent manner in chicken muscles.