title: Relative contribution of adipose triglyceride lipase and hormone-sensitive lipase to tumor necrosis factor-α (TNF-α)-induced lipolysis in adipocytes.
abstract: TNF-α potently stimulates basal lipolysis in adipocytes, which may contribute to hyperlipidemia and peripheral insulin resistance in obesity. Recent studies show that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) act sequentially in catalyzing the first two steps of adipose lipolysis in response to β-adrenergic stimulation. Here, we sought to determine their functional roles in TNF-α-induced lipolysis. Silencing of ATGL expression in adipocytes almost completely abolished basal and TNF-α-induced glycerol release. In comparison, the glycerol release under the same conditions was only partially decreased upon reduction in expression of either HSL or the ATGL coactivator CGI-58. Interestingly, overexpression of ATGL restored the lipolytic rates in cells with silenced HSL or CGI-58, indicating a predominant role for ATGL. While expression of ATGL, HSL and CGI-58 remains mostly unaffected, TNF-α treatment caused a rapid abrogation of the ATGL inhibitory protein G0S2. TNF-α drastically decreased the level of G0S2 mRNA, and the level of G0S2 protein could be maintained by inhibiting proteasomal protein degradation using MG-132. Furthermore, coexpression of G0S2 was able to significantly decrease TNF-α-stimulated lipolysis mediated by overexpressed ATGL or CGI-58. We propose that the early reduction in G0S2 content is permissive for TNF-α-induced lipolysis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, Arizona 85259, USA.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Bradlee L
authors.initials: BL
authors.lastname: Heckmann
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D041721:3T3-L1 Cells; D000256:Adenoviridae / Q000235:genetics; D000273:Adipose Tissue / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D008049:Lipase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D002787:Sterol Esterase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D018797:Cell Cycle Proteins; D008049:Lipase; D034741:RNA, Small Interfering; D002787:Sterol Esterase; D014409:Tumor Necrosis Factor-alpha; C508072:G0S2 protein, mouse; C492986:Abhd5 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases