Adiponectin is sufficient, but not required, for exercise‐induced increases in the expression of skeletal muscle mitochondrial enzymes

Abstract

Key pointsr Adiponectin is a regulator of skeletal muscle mitochondrial biogenesis. Previous research using the ob/ob mouse (leptin deficient, low adiponectin) has suggested that the presence of adipokines, including adiponectin, is necessary for exercise-induced increases in mitochondrial content.r In the current study, we examined the importance of adiponectin as a regulator of skeletal muscle mitochondrial content in response to exercise by comparing wildtype and adiponectin deficient mice.r Adiponectin deficient mice showed no differences in resting V O 2 , RER, or time to exhaustion during exercise when compared to wildtype mice. There were no differences in various protein markers of mitochondrial content.r A single bout of treadmill running increased the mRNA expression of mitochondrial proteins similarly in wildtype and adiponectin deficient mice. Chronic exercise (8 weeks) also increased the protein content of mitochondrial markers similarly in wildtype and adiponectin deficient mice.r We conclude that Ad is not required for exercise-induced increases in muscle mitochondrial proteins.Abstract Adiponectin (Ad) has been proposed to be a regulator of mitochondrial biogenesis in skeletal muscle, and necessary for exercise-induced increases in mitochondrial content. We first confirmed that Ad could acutely increase the expression of mitochondrial proteins during a 10 h incubation in isolated soleus and extensor digitorum longus (EDL) muscles. Next, we further examined the role of Ad as a regulator of mitochondrial content using Ad knockout (AdKO) mice. The AdKO animals showed no differences in resting V O 2 , respiratory exchange ratio, or in time to exhaustion during exercise when compared to wild-type (WT) mice. There was a reduction in resting palmitate oxidation in isolated soleus from AdKO animals (−23%, P < 0.05) but not EDL, and 5-aminoimidazole-4-carboxamide (AICAR)-stimulated palmitate oxidation was similar in both genotypes regardless of muscle. There were no differences in protein markers of mitochondrial content (COX4, CORE1, CS, PDHE1α) in red and white gastrocnemius between WT and AdKO animals. A single bout of treadmill running increased the phosphorylation of AMP-activated protein kinase (AMPK) and the mRNA expression of mitochondrial proteins in red and white gastrocnemius in both WT and AdKO animals, with no differences between genotypes. Finally, 8 weeks of chronic exercise training increased the protein content of mitochondrial markers similarly (ß25-35%) in red gastrocnemius from both WT and AdKO mice. Collectively, our results demonstrate that the absence of Ad is not accompanied

Adiponectin is not required for exercise training-induced improvements in glucose and insulin tolerance in mice

“…The absence of adiponectin in muscle (red gastrocnemius), adipose tissue (eWAT), and serum was confirmed and reported previously (Ritchie et al. ).…”

“…However, we have recently shown that exercise‐induced increases in mitochondrial protein expression are indistinguishable in skeletal muscle from WT and AdKO mice (Ritchie et al. ). Although this strongly suggests that Ad is not necessary for mitochondrial adaptations to exercise training, it is possible that Ad could be required for exercise training‐ induced improvements in insulin sensitivity.…”

Exercise prevents HFD- and OVX-induced type 2 diabetes risk factors by decreasing fat storage and improving fuel utilization

“…Alternatively, while the in vivo insulin injection protocol used in the current study is widely used throughout the field (Ritchie et al. ; Hamilton et al. ; MacDonald et al.…”

6‐Gingerol Improves Ectopic Lipid Accumulation, Mitochondrial Dysfunction, and Insulin Resistance in Skeletal Muscle of Ageing Rats: Dual Stimulation of the AMPK/PGC‐1α Signaling Pathway via Plasma Adiponectin and Muscular AdipoR1

“…Ageing reduces mitochondrial biogenesis and function, which are effects that have been associated with lower skeletal muscle AdipoR1 and AMPK activity . In C2C12 muscle cells, adiponectin increases the expression and activation of peroxisome proliferator activated receptor γ coactivator (PGC)‐1α, a key regulator of mitochondrial biogenesis, via AMPK signaling . Moreover, overexpression of PGC‐1α not only ameliorates mitochondrial biogenesis in mammalian tissues but also induces a fast‐ to slow‐fiber type conversion and activates genes of mitochondrial oxidative metabolism in skeletal muscle …”