Abstract
A main function of white adipose tissue is to release fatty acids from stored triacylglycerol for other tissues to use as an energy source. Whereas endocrine regulation of lipolysis has been extensively studied, autocrine and paracrine regulation is not well understood. Here we describe the role of the newly identified major adipocyte phospholipase A2, AdPLA (encoded by Pla2g16, also called HREV107), in the regulation of lipolysis and adiposity. AdPLA-null mice have a markedly higher rate of lipolysis owing to increased cyclic AMP levels arising from the marked reduction in the amount of adipose prostaglandin E2 that binds the Gαi-coupled receptor, EP3. AdPLA-null mice have markedly reduced adipose tissue mass and triglyceride content but normal adipogenesis. They also have higher energy expenditure with increased fatty acid oxidation within adipocytes. AdPLA-deficient ob/ob mice remain hyperphagic but lean, with increased energy expenditure, yet have ectopic triglyceride storage and insulin resistance. AdPLA is a major regulator of adipocyte lipolysis and is crucial for the development of obesity.
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Acknowledgements
This work was supported in part by DK75682 from the US National Institutes of Health to H.S.S. and DK59635 to G.I.S. R.E.D. and K.A.V. are recipients of postdoctoral fellowships from the Natural Sciences and Engineering Research Council of Canada. R.E.D. is a recipient of a postdoctoral fellowship from the Canadian Institutes of Health Research. The authors would like to thank O. Barauskas for technical help; D. Frasson for fatty acid oxidation measurement; Y. Wang for performing WR1339 injections; J. Lu, J. Chen, R. Mantara and N. Nag for assistance with animal maintenance; A. Birkenfled and D. Frederick for assistance with clamping studies; C. Lange and J. Chithalen for assistance with graphics; and Merck Frosst Canada for the kind gift of L826266.
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Jaworski, K., Ahmadian, M., Duncan, R. et al. AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency. Nat Med 15, 159–168 (2009). https://doi.org/10.1038/nm.1904
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DOI: https://doi.org/10.1038/nm.1904
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