title: Lipolysis in the absence of hormone-sensitive lipase: evidence for a common mechanism regulating distinct lipases.
abstract: Hormone-sensitive lipase (HSL) is presumed to be essential for lipolysis, which is defined as the mobilization of free fatty acids from adipocytes. In the present study, we investigated the effects of various lipolytic hormones on the lipolysis in adipocytes derived from mouse embryonic fibroblasts (MEF adipocytes) prepared from HSL-deficient mice (HSL-/-). HSL-/- MEF differentiated into mature adipocytes in a manner indistinguishable from that of wild-type mice. Both isoproterenol (ISO) and tumor necrosis factor (TNF)-alpha stimulated the rate of lipolysis in HSL-/- MEF adipocytes, although to a lesser extent than in wild-type cells, and these lipolytic activities were inhibited by H-89, a cAMP-dependent protein kinase inhibitor, and troglitazone, respectively. Thus, the responses of the residual lipolytic activity to lipolytic hormones and TNF-alpha were well conserved in the absence of HSL. Extracts from HSL-/- MEF adipocytes hydrolyzed triacylglycerol (TG) but not cholesterol ester, indicating that the residual lipolytic activity was mediated by another TG-specific lipase. The TG lipase activity, which was decreased in cytosolic fraction in response to ISO, was increased in fat cake fraction. Therefore, translocation of the TG lipase may explain, at least partially, the ISO-stimulated lipolysis in HSL-/- adipocytes. In conclusion, lipolysis is mediated not only by HSL but also by the non-HSL TG lipase, whose responses to lipolytic hormones are similar to those of HSL. We propose that both lipases are regulated by common mechanism of lipolysis.
authors.affiliation: Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Naoya
authors.initials: N
authors.lastname: Yahagi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tomita
authors.forename: Futoshi
authors.initials: F
authors.lastname: Shionoiri
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Harada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Takanari
authors.initials: T
authors.lastname: Gotoda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
mesh_terms: D017667:Adipocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002839:Chromans / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006868:Hydrolysis / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008049:Lipase / Q000502:physiology; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D002787:Sterol Esterase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013449:Sulfonamides; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014020:Tissue Extracts / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002839:Chromans; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D013844:Thiazoles; D045162:Thiazolidinediones; D014020:Tissue Extracts; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D017868:Cyclic AMP-Dependent Protein Kinases; D002787:Sterol Esterase; D008049:Lipase; D000077288:Troglitazone; D007545:Isoproterenol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide