Rondini_2017_J.Pharmacol.Exp.Ther_363_367

Reference

Title : Novel Pharmacological Probes Reveal ABHD5 as a Locus of Lipolysis Control in White and Brown Adipocytes - Rondini_2017_J.Pharmacol.Exp.Ther_363_367
Author(s) : Rondini EA , Mladenovic-Lucas L , Roush WR , Halvorsen GT , Green AE , Granneman JG
Ref : Journal of Pharmacology & Experimental Therapeutics , 363 :367 , 2017
Abstract :

Current knowledge regarding acute regulation of adipocyte lipolysis is largely based on receptor-mediated activation or inhibition of pathways that influence intracellular levels of cAMP, thereby affecting protein kinase A (PKA) activity. We recently identified synthetic ligands of alpha-beta-hydrolase domain containing 5 (ABHD5) that directly activate adipose triglyceride lipase (ATGL) by dissociating ABHD5 from its inhibitory regulator, perilipin-1 (PLIN1). In the current study, we used these novel ligands to determine the direct contribution of ABHD5 to various aspects of lipolysis control in white (3T3-L1) and brown adipocytes. ABHD5 ligands stimulated adipocyte lipolysis without affecting PKA-dependent phosphorylation on consensus sites of PLIN1 or hormone-sensitive lipase (HSL). Cotreatment of adipocytes with synthetic ABHD5 ligands did not alter the potency or maximal lipolysis efficacy of the beta-adrenergic receptor (ADRB) agonist isoproterenol (ISO), indicating that both target a common pool of ABHD5. Reducing ADRB/PKA signaling with insulin or desensitizing ADRB suppressed lipolysis responses to a subsequent challenge with ISO, but not to ABHD5 ligands. Lastly, despite strong treatment differences in PKA-dependent phosphorylation of HSL, we found that ligand-mediated activation of ABHD5 led to complete triglyceride hydrolysis, which predominantly involved ATGL, but also HSL. These results indicate that the overall pattern of lipolysis controlled by ABHD5 ligands is similar to that of isoproterenol, and that ABHD5 plays a central role in the regulation of adipocyte lipolysis. As lipolysis is critical for adaptive thermogenesis and in catabolic tissue remodeling, ABHD5 ligands may provide a means of activating these processes under conditions where receptor signaling is compromised.

PubMedSearch : Rondini_2017_J.Pharmacol.Exp.Ther_363_367
PubMedID: 28928121
Gene_locus related to this paper: human-ABHD5 , mouse-abhd5

Related information

Inhibitor SR-3420    SR-4995    SR-4559
Gene_locus SR-3420    SR-4995    SR-4559    human-ABHD5    mouse-abhd5
Family SR-3420    SR-4995    SR-4559    human-ABHD5    mouse-abhd5    abh_upf0017

Citations formats

Rondini EA, Mladenovic-Lucas L, Roush WR, Halvorsen GT, Green AE, Granneman JG (2017)
Novel Pharmacological Probes Reveal ABHD5 as a Locus of Lipolysis Control in White and Brown Adipocytes
Journal of Pharmacology & Experimental Therapeutics 363 :367

Rondini EA, Mladenovic-Lucas L, Roush WR, Halvorsen GT, Green AE, Granneman JG (2017)
Journal of Pharmacology & Experimental Therapeutics 363 :367