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Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction - PubMed

  • ️Sun Jan 01 2017

Review

Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction

Arunkumar E Achari et al. Int J Mol Sci. 2017.

Abstract

Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can also produce this adipocytokine. Adiponectin effects are mediated by adiponectin receptors, which occur as two isoforms (AdipoR1 and AdipoR2). Adiponectin has direct actions in liver, skeletal muscle, and the vasculature.Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Several endoplasmic reticulum ER-associated proteins, including ER oxidoreductase 1-α (Ero1-α), ER resident protein 44 (ERp44), disulfide-bond A oxidoreductase-like protein (DsbA-L), and glucose-regulated protein 94 (GPR94), have recently been found to be involved in the assembly and secretion of higher-order adiponectin complexes. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in metabolic tissues. Studies have shown that adiponectin administration in humans and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects, and, in certain settings, also decreases body weight. Therefore, adiponectin replacement therapy in humans may suggest potential versatile therapeutic targets in the treatment of obesity, insulin resistance/type 2 diabetes, and atherosclerosis. The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review.

Keywords: adiponectin; endothelial dysfunction; obesity; type 2 diabetes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Domains and structure of adiponectin: Full-length adiponectin is composed of 244 amino acids, including a collagen-like fibrous domain at the N-terminus and a C1q-like globular domain at the C-terminus. In circulation, adiponectin forms low-molecular weight (LMW) homotrimers and hexamers, and high-molecular weight (HMW) multimers of 12–18 monomers. A smaller form of adiponectin that consists of globular domain also exists in plasma in negligible amounts. Each adiponectin subunit in the basic trimeric building block represented in a different color.

Figure 2
Figure 2

Schematic representation of adiponectin signal transduction implicating a cross talk with the insulin signaling pathway: Insulin and adiponectin interact with their respective receptors, which trigger a cascade of signaling events. Metabolic actions of the insulin are mainly carried out by PI3K/AKT pathway, resulting in increased protein synthesis, lipogenesis, glucose uptake and utilization, glycogen synthesis, and reduced lipolysis and gluconeogenesis. Interaction of adiponectin with its receptors (Adipo R1 and R2) results in the activation of multiple signaling pathways including IRS1/2, AMPK, and p38 MAPK. Activation of IRS1/2 by adiponectin signaling is a major mechanism by which adiponectin sensitizes insulin action in insulin responsive tissues.

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References

    1. Ghoshal K., Bhattacharyya M. Adiponectin: Probe of the molecular paradigm associating diabetes and obesity. World J. Diabetes. 2015;6:151–166. doi: 10.4239/wjd.v6.i1.151. - DOI - PMC - PubMed
    1. Scherer P.E., Williams S., Fogliano M., Baldini G., Lodish H.F. A novel serum protein similar to c1q, produced exclusively in adipocytes. J. Biol. Chem. 1995;270:26746–26749. doi: 10.1074/jbc.270.45.26746. - DOI - PubMed
    1. Maeda K., Okubo K., Shimomura I., Funahashi T., Matsuzawa Y., Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apm1 (adiposemost abundant gene transcript 1) Biochem. Biophys. Res. Commun. 1996;221:286–289. doi: 10.1006/bbrc.1996.0587. - DOI - PubMed
    1. Nakano Y., Tobe T., Choi-Miura N.-H., Mazda T., Tomita M. Isolation and characterization of gbp28, a novel gelatin-binding protein purified from human plasma. J. Biochem. 1996;120:803–812. doi: 10.1093/oxfordjournals.jbchem.a021483. - DOI - PubMed
    1. Yamauchi T., Kamon J., Waki H., Terauchi Y., Kubota N., Hara K., Mori Y., Ide T., Murakami K., Tsuboyama-Kasaoka N. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 2001;7:941–946. doi: 10.1038/90984. - DOI - PubMed

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