Regulation of metabolism - Role of Adiponectin in regulation of metabolism

Role of Adiponectin in regulation of metabolism

Absract:

Adiponectin, an adipokine secreted by the white adipose tissue, plays an important role in regulating glucose and lipid metabolism and controlling energy homeostasis in insulin-sensitive tissues.

Details:

Adiponectin, an adipokine secreted by the white adipose tissue, plays an important role in regulating glucose and lipid metabolism and controlling energy homeostasis in insulin-sensitive tissues [1].

Adiponectin binding to AdipoR1 and AdipoR2 activates APPL [1], [2]. APPL binds to and activates LKB1 and promotes LKB1 binding to AMPK alpha subunit [3], [4]. Adiponectin-induced AMPK alpha subunit probably activates p38alpha (MAPK14) signaling [5], result in stimulation of PPARGC1 (PGC1-alpha) and PPAR-alpha [6], [7], [8]. PPARGC1 (PGC1-alpha) activation requires deacetylation by Sirtuin1 [8]. PPARGC1 (PGC1-alpha) probably promotes transcription of genes, involved in mitochondrial biogenesis, inhibition of reactive oxygen species production and fatty acid beta-oxidation: TFAM, SOD2, ACADM [8]. Adiponectin-activated PPAR-alpha forms complex PPAR-alpha/RXR-alpha [9]. PPAR-alpha/RXR-alpha promotes transcription of genes, involved in fatty acid beta-oxidation and fatty acid transport: CPT-1A and CPT-1B, ACOX1 and H-FABP [5], [7].

Adiponectin-induced AMPK alpha subunit inhibits ACACA-dependent production of Malonyl-CoA [5]. Reduction in levels of Malonyl-CoA results in attenuation of Malonyl-CoA-induced inhibition of CPT-1A and CPT-1B [7], leading to stimulation of fatty acid beta-oxidation.

Adiponectin inhibits SREBP1 precursor in a LKB1/ AMPK alpha subunit-dependent manner, results in negative regulation of lipid biosynthetic process [10].

Adiponectin stimulate activation of Insulin processed signaling cascade. Adiponectin-stimulated APPL binds to PI3K cat class IA (p110-alpha) and AKT2 [11], and thereby increases Insulin processed-induced AKT2 activation and GLUT4 translocation [1], [12]. Also, Adiponectin-induced AMPK alpha subunit phosphorylates Tuberin. Activated Tuberin together with Hamartin inhibit RHEB2/ Raptor/ mTOR signaling cascade, result in inhibition of p70 S6 kinase1. Inhibition of p70 S6 kinase1 leads to reduced phosphorylation of IRS-1 [3]. Thus Adiponectin augments Insulin processed signaling through Insulin receptor and IRS-1.

Adiponectin-induced APPL binds to and activate Rab-5A, result in increase in GLUT4 translocation [12].

Adiponectin-activated AMPK alpha subunit phosphorylates and inhibits TORC2 [13]. Suppression of TORC2 leads to reduced expression of CREB1, G6PT and PPCKC, resulting in inhibition of glucose metabolic process [14], [15], [16].

Objects list:

References:

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