Diet-induced insulin resistance in mice lacking adiponectin/ACRP30

Abstract

Here we investigated the biological functions of adiponectin/ACRP30, a fat-derived hormone, by disrupting the gene that encodes it in mice. Adiponectin/ACRP30-knockout (KO) mice showed delayed clearance of free fatty acid in plasma, low levels of fatty-acid transport protein 1 (FATP-1) mRNA in muscle, high levels of tumor necrosis factor-alpha (TNF-alpha) mRNA in adipose tissue and high plasma TNF-alpha concentrations. The KO mice exhibited severe diet-induced insulin resistance with reduced insulin-receptor substrate 1 (IRS-1)-associated phosphatidylinositol 3 kinase (PI3-kinase) activity in muscle. Viral mediated adiponectin/ACRP30 expression in KO mice reversed the reduction of FATP-1 mRNA, the increase of adipose TNF-alpha mRNA and the diet-induced insulin resistance. In cultured myocytes, TNF-alpha decreased FATP-1 mRNA, IRS-1-associated PI3-kinase activity and glucose uptake, whereas adiponectin increased these parameters. Our results indicate that adiponectin/ACRP30 deficiency and high TNF-alpha levels in KO mice reduced muscle FATP-1 mRNA and IRS-1-mediated insulin signaling, resulting in severe diet-induced insulin resistance.

Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells

“…We subsequently investigated the effects of gAd on glucose uptake and metabolism in these cells. Consistent with previous observations in rat skeletal muscle and C 2 C 12 myocytes [6,10,11], gAd increased glucose uptake in L6 myotubes. Importantly, we have demonstrated that gAd increases glucose uptake by increasing the cell surface content of GLUT4myc.…”

“…Previous studies have reported that adiponectin increases glucose uptake in muscle cells [6,10,11] and fat cells [27], but few have examined the subsequent metabolism of glucose. Potential pathways of glucose metabolism in muscle cells include glycogen synthesis, glucose oxidation and lactate production [28].…”

“…Injection of adiponectin into rodents has been shown to decrease resting blood glucose levels and protect animals with dietinduced obesity from developing insulin resistance [6][7][8][9]. Treatment of isolated skeletal muscle or C 2 C 12 myocytes with adiponectin stimulates glucose transport [6,10,11], suggesting that this may be one mechanism by which adiponectin acts to alleviate hyperglycaemia. However, very little is known about the molecular mechanism by which adiponectin stimulates glucose uptake.…”

Different actions of losartan and ramipril on adipose tissue activity and vascular remodeling biomarkers in hypertensive patients

“…31 Ablation of the ADN gene in mice results in insulin resistance, glucose intolerance, dyslipidemia and increased susceptibility to vascular injury and atherosclerosis. [32][33][34] Adiponectin reverses these abnormalities by stimulating oxidation of fatty acids, suppressing gluconeogenesis, inhibiting monocyte adhesion and inhibiting macrophage transformation, as well as proliferation and migration of smooth muscle cells in blood vessels. 17,32,35 In our study, we observed an improvement in both insulin resistance and adiponectinemia in losartan-treated patients.…”

Bioinformatic identification of genes encoding C1q-domain-containing proteins in zebrafish

“…These C1qDC proteins have extremely diverse functions, such as acting like hormones (Takamatsu et al, 1993;Maeda et al, 2002), contributing to the interaction of the cell with extracellular matrices (Tom Tang et al, 2005), recognizing targets for several immunological processes (Navratil et al, 2001), or connecting a single calcified otolith to the sensory epithelium (Murayama et al, 2002). In human, a total of 31 independent C1qDC gene sequences have been screened from the human genome.…”