Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1

Abstract

Adiponectin is an anti-diabetic adipokine. Its receptors possess a seven-transmembrane topology with the amino terminus located intracellularly, which is the opposite of G-protein-coupled receptors. Here we provide evidence that adiponectin induces extracellular Ca(2+) influx by adiponectin receptor 1 (AdipoR1), which was necessary for subsequent activation of Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta), AMPK and SIRT1, increased expression and decreased acetylation of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), and increased mitochondria in myocytes. Moreover, muscle-specific disruption of AdipoR1 suppressed the adiponectin-mediated increase in intracellular Ca(2+) concentration, and decreased the activation of CaMKK, AMPK and SIRT1 by adiponectin. Suppression of AdipoR1 also resulted in decreased PGC-1alpha expression and deacetylation, decreased mitochondrial content and enzymes, decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance. Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes.

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.…”

“…Chronic activation of AMP kinase can result in enhanced mitochondrial biogenesis and oxidative capacity [33]. AD can stimulate glucose utilization and fatty acid oxidation by activating AMP-activated protein kinase [11,34]. Our study demonstrated that CIH partially inhibited the expression of AMPK pathway, whereas AD supplementation could imminently elevate the expression of LKB1 (AMPKK)/AMPK/PGC1-a.…”

STEAP1 Is Associated with the Invasive and Oxidative Stress Phenotype of Ewing Tumors

“…We choose MMP-1, ADIPOR1, and DTX3L for follow-up due to their high expression in Ewing tumors and their involvement in oxidative stress responses (34,38,39). Notably, (Fig.…”

Mechanisms of lifespan extension and preventive effects of calorie restriction on tumor development: Possible link between central neuroendocrine system and peripheral metabolic adaptation

“…On the other hand, the activity of PGC-1α is probably directly modulated through pathways that depend on sirtuin 1 (SIRT1), an NAD + -dependent deacetylase [27][28][29] . PGC-1α could interact with and activate various kinds of transcription factors, and regulate expression of various metabolism-related genes 25) .…”