Suppression of adipose lipolysis by long-chain fatty acid analogs.

Journal of Lipid Research
Bella KalderonJacob Bar-Tana

Abstract

Agonist-induced lipolysis of adipose fat is robustly inhibited by insulin or by feedback inhibition by the long-chain fatty acids (LCFA) produced during lipolysis. However, the mode of action of LCFA in suppressing adipose lipolysis is not clear. β,β'-Tetramethyl hexadecanedioic acid (Mββ/ EDICA16) is a synthetic LCFA that is neither esterified into lipids nor β-oxidized, and therefore, it was exploited for suppressing agonist-induced lipolysis in analogy to natural LCFA. Mββ is shown here to suppress isoproterenol-induced lipolysis in the rat in vivo as well as in 3T3-L1 adipocytes. Inhibition of isoproterenol-induced lipolysis is due to decrease in isoproterenol-induced cAMP with concomitant inhibition of the phosphorylation of hormone-sensitive lipase and perilipin by protein kinase A. Suppression of cellular cAMP levels is accounted for by inhibition of the adenylate cyclase due to suppression of Raf1 expression by Mββ-activated AMPK. Suppression of Raf1 is further complemented by induction of components of the unfolded-protein-response by Mββ. Our findings imply genuine inhibition of agonist-induced adipose lipolysis by LCFA, independent of their β-oxidation or reesterification. Mββ suppression of agonist-induced lipolysis...Continue Reading

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Citations

Mar 21, 2013·Obesity·Irene O C M VroegrijkVanessa van Harmelen
Jun 7, 2017·Journal of Lipid Research·Santhosh SatapatiJin Shang
Mar 7, 2020·Genes & Development·Rabih El-MerahbiGrzegorz Sumara
Aug 24, 2013·Endocrine Reviews·Einav Yehuda-ShnaidmanJacob Bar-Tana
Feb 2, 2019·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Marcelo Flores-OpazoDavid Stapleton
Mar 9, 2017·American Journal of Physiology. Endocrinology and Metabolism·Michael ValitskyJacob Bar-Tana
Jul 23, 2020·Cancer & Metabolism·Sophia EldadJacob Bar-Tana
Oct 23, 2020·Molecular Metabolism·Anna Sofie HustedThue W Schwartz
Jul 15, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Einav HubelOren Shibolet

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