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Novel role for adiponectin pathway in human skeletal muscle bioenergetics
Author(s) -
Civitarese AE,
Nawrocki AR,
Ukropcova B,
Carling S,
Hulver M,
DeFronzo RA,
Mandarino L,
Scherer P,
Smith SR,
Ravussin E
Publication year - 2006
Publication title -
obesity reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.845
H-Index - 162
eISSN - 1467-789X
pISSN - 1467-7881
DOI - 10.1111/j.1467-7881.2006.00280_8.x
Subject(s) - adiponectin , medicine , mitochondrial biogenesis , endocrinology , citrate synthase , skeletal muscle , mitochondrion , bioenergetics , biology , insulin resistance , oxidative phosphorylation , adiponectin receptor 1 , chemistry , insulin , microbiology and biotechnology , biochemistry , enzyme
Insulin resistance in skeletal muscle is associated with impaired oxidative capacity and reduced size, number and function of mitochondria. Insulin‐resistant individuals have lower adiponectin concentrations, a characteristic predating the development of type‐2 diabetes (T2D). The aim of this study was to test the potential role of adiponectin in mitochondrial bioenergetics in individuals predisposed to develop T2D, in adiponectin KO mice and in primary muscle cell culture. Individuals with a family history of T2D displayed lower plasma adiponectin concentration ( P = 0.03), reduced PGC1β ( P = 0.04) and mtFAM ( P = 0.03) mRNA, lower mitochondrial content ( P = 0.006), citrate synthase ( P = 0.02) and (‐HAD ( P = 0.03) activity, suggesting defective mitochondrial bioenergetics in skeletal muscle. In addition, AdipoR1 was the principle correlate of mitochondrial content ( r 2 = 0.81), suggesting an important role in mitochondrial biogenesis. Knock out of adiponectin in mice was associated with low PGC1α and PPARδ mRNA (both, P < 0.05), reduced mitochondrial content ( P < 0.05) and COX II activity ( P < 0.05) and markers for type‐1 oxidative fibers in skeletal muscle. This suggests that mitochondrial function is dependent on circulating adiponectin. In primary cultures of human myotubes, treatment with adiponectin induced AMPKK/ AMPK activity, PGC1α protein, mitochondrial biogenesis ( P < 0.05), palmitate oxidation ( P < 0.05), citrate synthase ( P < 0.05) and SOD activity ( P < 0.05), and reduced mitochondrial membrane potential and the production of ROS ( P < 0.05). The inhibition of adiponectin receptor expression by siRNA or of AMPK by a pharmacological agent blunted the induction in mitochondrial function. Our findings indicate a novel pathway in skeletal muscle by which adiponectin increase mitochondrial number and function and exerts an insulin sensitizing effect.