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|Title:||Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin||Authors:||Holland, W.L.
|Issue Date:||Jan-2011||Citation:||Holland, W.L., Miller, R.A., Wang, Z.V., Sun, K., Barth, B.M., Bui, H.H., Davis, K.E., Bikman, B.T., Halberg, N., Rutkowski, J.M., Wade, M.R., Tenorio, V.M., Kuo, M.-S., Brozinick, J.T., Zhang, B.B., Birnbaum, M.J., Summers, S.A., Scherer, P.E. (2011-01). Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nature Medicine 17 (1) : 55-63. ScholarBank@NUS Repository. https://doi.org/10.1038/nm.2277||Abstract:||The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival. No unifying mechanism has yet explained how adiponectin can exert such a variety of beneficial systemic effects. Here, we show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, AdipoR1 and AdipoR2, and enhances ceramide catabolism and formation of its antiapoptotic metabolite-sphingosine-1-phosphate (S1P)independently of AMP-dependent kinase (AMPK). Using models of inducible apoptosis in pancreatic beta cells and cardiomyocytes, we show that transgenic overproduction of adiponectin decreases caspase-8-mediated death, whereas genetic ablation of adiponectin enhances apoptosis in vivo through a sphingolipid-mediated pathway. Ceramidase activity is impaired in cells lacking both adiponectin receptor isoforms, leading to elevated ceramide levels and enhanced susceptibility to palmitate-induced cell death. Combined, our observations suggest a unifying mechanism of action for the beneficial systemic effects exerted by adiponectin, with sphingolipid metabolism as its core upstream signaling component. © 2011 Nature America, Inc. All rights reserved.||Source Title:||Nature Medicine||URI:||http://scholarbank.nus.edu.sg/handle/10635/126542||ISSN:||10788956||DOI:||10.1038/nm.2277|
|Appears in Collections:||Staff Publications|
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