Role of adiponectin in human skeletal muscle bioenergetics

Abstract

Insulin resistance is associated with impaired skeletal muscle oxidation capacity and reduced mitochondrial number and function. Here, we report that adiponectin signaling regulates mitochondrial bioenergetics in skeletal muscle. Individuals with a family history of type 2 diabetes display skeletal muscle insulin resistance and mitochondrial dysfunction; adiponectin levels strongly correlate with mtDNA content. Knockout of the adiponectin gene in mice is associated with insulin resistance and low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle. Adiponectin treatment of human myotubes in primary culture induces mitochondrial biogenesis, palmitate oxidation, and citrate synthase activity, and reduces the production of reactive oxygen species. The inhibition of adiponectin receptor expression by siRNA, or of AMPK by a pharmacological agent, blunts adiponectin induction of mitochondrial function. Our findings define a skeletal muscle pathway by which adiponectin increases mitochondrial number and function and exerts antidiabetic effects.

Adiponectin alleviates genioglossal mitochondrial dysfunction in rats exposed to intermittent hypoxia

“…The current study revealed that AD supplementation could reverse hypoadiponectinemia and mitochondrial dysfunction associated with CIH [3]. Anthony E. and other studies have shown that AD could increase PGC1-a expression to promote mitochondrial content in skeletal muscle cells [9,11]. Consistent with our results, AD supplementation could promote GG mitochondrial synthesis even under CIH conditions.…”

“…In our study, we clearly demonstrated that exogenous AD supplementation could enhance the activity of cytochrome oxidase and succinate dehydrogenase, and improve the mRNA levels of Hmox1, Cs, Cox4i1, Ant1, OGG1 and of NQO1. Anthony E. et al found that AD could additionally switch type II fibers into type I fibers [9]. Our finding also showed that AD could significantly increase the expression level of PGC1-a.…”

“…Adiponectin can activate the LKB1/AMPK/PGC1-a signaling pathway, which has impact on mitochondrial contents and function [9]. Therefore, we examined the effect of CIH and CIH+AD on AMPK activation.…”

Liver function parameters, cholesterol, and phospholipid α-linoleic acid are associated with adipokine levels in overweight and obese adults

“…12 [14][15][16][17]. Elevations in these enzymes have been associated with non-alcoholic fatty liver disease.…”

“…This hormone has many regulatory actions on energy homeostasis, glucose balance, and fatty acid metabolism, and it enhances glucose metabolism in the liver and skeletal muscle [14][15][16][17].…”