Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1.
Nature 2010;464:1313-9
Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, Yamaguchi M, Namiki S, Nakayama R, Tabata M, Ogata H, Kubota N, Takamoto I, Hayashi YK, Yamauchi N, Waki H, Fukayama M, Nishino I, Tokuyama K, Ueki K, Oike Y, Ishii S, Hirose K, Shimizu T, Touhara K, Kadowaki T
This mechanistic study was performed to examine whether adiponectin/AdipoR1 signalling could be associated with mitochondrial dysfunction. For that purpose, muscle-specific Adipor1-knockout (muscle-RIKO) mice were used to study the signalling mechanisms by which adiponectin/AdipoR1 would induce their biological effects. Results showed that suppression of AdipoR1 resulted in decreased peroxisome proliferator-activated recepto y coactivator-1alpha (PGC-1alpha) expression and deacetylation, which is a key regulator of mitochondrial content and function. It was also observed that adiponectin and AdipoR1 increase PGC-1alpha expression and activity by inducing extracellular Ca2+ influx as well as by activating AMPK and SIRT1 which lead to increased mitochondrial biogenesis. Moreover, the authors found that in skeletal muscle, AdipoR1 regulated insulin sensitivity by several mechanisms such as activation of S6 kinase 1, increasing oxidative stress and increasing triglyceride content. Thus, these results suggest that AdipoR1 has a significant role in the various physiological effects of adiponectin in the skeletal muscle.
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