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Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores
Authors:Lass Achim  Zimmermann Robert  Oberer Monika  Zechner Rudolf
Institution:Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria
Abstract:Lipolysis is the biochemical pathway responsible for the catabolism of triacylglycerol (TAG) stored in cellular lipid droplets. The hydrolytic cleavage of TAG generates non-esterified fatty acids, which are subsequently used as energy substrates, essential precursors for lipid and membrane synthesis, or mediators in cell signaling processes. Consistent with its central importance in lipid and energy homeostasis, lipolysis occurs in essentially all tissues and cell types, it is most abundant, however, in white and brown adipose tissue. Over the last 5years, important enzymes and regulatory protein factors involved in lipolysis have been identified. These include an essential TAG hydrolase named adipose triglyceride lipase (ATGL) annotated as patatin-like phospholipase domain-containing protein A2], the ATGL activator comparative gene identification-58 annotated as α/β hydrolase containing protein 5], and the ATGL inhibitor G0/G1 switch gene 2. Together with the established hormone-sensitive lipase annotated as lipase E] and monoglyceride lipase, these proteins constitute the basic "lipolytic machinery". Additionally, a large number of hormonal signaling pathways and lipid droplet-associated protein factors regulate substrate access and the activity of the "lipolysome". This review summarizes the current knowledge concerning the enzymes and regulatory processes governing lipolysis of fat stores in adipose and non-adipose tissues. Special emphasis will be given to ATGL, its regulation, and physiological function.
Keywords:2-AG  2-arachidonoyl glycerol  ABHD1-15  α/β hydrolase domain containing protein 1-15  ARF1  ADP-ribosylation factor 1  ATGL  adipose triglyceride lipase  BAT  brown adipose tissue  BiFC  bimolecular fluorescence complementation  CDS  Chanarin-Dorfman syndrome  CE  cholesterylester  CGI-58  comparative-gene-identification 58  COPI  coat protein complex-I  cPLA2  cytosolic phospholipase A2  DAG  diacylglycerol  ER  endoplasmic reticulum  FoxO1  forkhead box O1  G0S2  G0/G1 Switch Protein 2  GS2  gene sequence 2  HSL  hormone-sensitive lipase  LD  lipid droplet  LPAAT  lysophosphatidic acid acyltransferase  MAG  monoacylglycerol  MGL  monoglyceride lipase  mTor  mammalian target of rapamycin  NEFA  non-esterified fatty acid  NLSD  neutral lipid storage disease  NLSDI  NLSD with ichthyosis  NLSDM  NLSD with myopathy  PKA  protein kinase A  PNPLA1-5  patatin-like phospholipase domain containing protein 1-5  PPARα/γ  peroxisome proliferator-activated receptor-alpha/gamma  PPRE  PPAR-response element  RBP4  retinol-binding protein 4  RE  retinylester  STS  steroid sulfatase  TAG  triacylglycerol  TGH  triglyceride hydrolase  TNF-α  tumor necrosis factor alpha  WAT  white adipose tissue
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