We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
NIA0002 Novel role for adiponectin pathway in human skeletal muscle bioenergetics.
- Authors
Civitarese, A. E.; Nawrocki, A. R.; Ukropcova, B.; Carling, S.; Hulver, M.; DeFronzo, R. A.; Mandarino, L.; Scherer, P.; Smith, S. R.; Ravussin, E.
- Abstract
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 ( r2 = 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.
- Subjects
INSULIN resistance; MUSCLE cells; MITOCHONDRIA; ORGANELLE formation; MESSENGER RNA; TYPE 2 diabetes
- Publication
Obesity Reviews, 2006, Vol 7, p37
- ISSN
1467-7881
- Publication type
Article
- DOI
10.1111/j.1467-7881.2006.00280_8.x