Lipolysis – A highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores

Progress in Lipid Research - Tập 50 - Trang 14-27 - 2011
Achim Lass1, Robert Zimmermann1, Monika Oberer1, Rudolf Zechner1
1Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria

Tài liệu tham khảo

Unger, 2010, Lipid homeostasis, lipotoxicity and the metabolic syndrome, Biochim Biophys Acta, 1801, 209, 10.1016/j.bbalip.2009.10.006 Slawik, 2006, Lipotoxicity, overnutrition and energy metabolism in aging, Ageing Res Rev, 5, 144, 10.1016/j.arr.2006.03.004 DeFronzo, 2004, Dysfunctional fat cells, lipotoxicity and type 2 diabetes, Int J Clin Pract Suppl, 9, 10.1111/j.1368-504X.2004.00389.x Lelliott, 2004, Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation, Int J Obes Relat Metab Disord, 28, S22, 10.1038/sj.ijo.0802854 Duncan, 2007, Regulation of lipolysis in adipocytes, Annu Rev Nutr, 27, 79, 10.1146/annurev.nutr.27.061406.093734 Langin, 2006, Control of fatty acid and glycerol release in adipose tissue lipolysis, CR Biol, 329, 598, 10.1016/j.crvi.2005.10.008 Zechner, 2005, Lipolysis: pathway under construction, Curr Opin Lipidol, 16, 333, 10.1097/01.mol.0000169354.20395.1c Lass, 2006, Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman syndrome, Cell Metab, 3, 309, 10.1016/j.cmet.2006.03.005 Holm, 2003, Molecular mechanisms regulating hormone-sensitive lipase and lipolysis, Biochem Soc Trans, 31, 1120, 10.1042/bst0311120 Zimmermann, 2004, Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase, Science, 306, 1383, 10.1126/science.1100747 Haemmerle, 2002, Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis, J Biol Chem, 277, 4806, 10.1074/jbc.M110355200 Osuga, 2000, Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity, Proc Natl Acad Sci USA, 97, 787, 10.1073/pnas.97.2.787 Karlsson, 1997, CDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases, J Biol Chem, 272, 27218, 10.1074/jbc.272.43.27218 Fischer, 2007, The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy, Nat Genet, 39, 28, 10.1038/ng1951 Schweiger, 2009, Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5, Am J Physiol Endocrinol Metab, 297, E289, 10.1152/ajpendo.00099.2009 Haemmerle, 2006, Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase, Science, 312, 734, 10.1126/science.1123965 Yang, 2010, The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase, Cell Metab, 11, 194, 10.1016/j.cmet.2010.02.003 Lu, 2010, Differential control of ATGL-mediated lipid droplet degradation by CGI-58 and G0S2, Cell Cycle, 9, 2719, 10.4161/cc.9.14.12181 Jenkins, 2004, Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities, J Biol Chem, 279, 48968, 10.1074/jbc.M407841200 Wilson, 2006, Characterization of the human patatin-like phospholipase family, J Lipid Res, 47, 1940, 10.1194/jlr.M600185-JLR200 Okazaki, 2002, Lipolysis in the absence of hormone-sensitive lipase: evidence for a common mechanism regulating distinct lipases, Diabetes, 51, 3368, 10.2337/diabetes.51.12.3368 Kinsey SG, Long JZ, Cravatt BF, Lichtman AH. Fatty acid amide hydrolase and monoacylglycerol lipase inhibitors produce anti-allodynic effects in mice through distinct cannabinoid receptor mechanisms. J Pain 2010; in press. Schlosburg, 2010, Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system, Nat Neurosci, 13, 1113, 10.1038/nn.2616 Long, 2009, Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo, Proc Natl Acad Sci USA, 106, 20270, 10.1073/pnas.0909411106 Pan, 2009, Blockade of 2-arachidonoylglycerol hydrolysis by selective monoacylglycerol lipase inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) enhances retrograde endocannabinoid signaling, J Pharmacol Exp Ther, 331, 591, 10.1124/jpet.109.158162 Long, 2009, Characterization of monoacylglycerol lipase inhibition reveals differences in central and peripheral endocannabinoid metabolism, Chem Biol, 16, 744, 10.1016/j.chembiol.2009.05.009 Kinsey, 2009, Blockade of endocannabinoid-degrading enzymes attenuates neuropathic pain, J Pharmacol Exp Ther, 330, 902, 10.1124/jpet.109.155465 Schlosburg, 2009, Inhibitors of endocannabinoid-metabolizing enzymes reduce precipitated withdrawal responses in THC-dependent mice, AAPS J, 11, 342, 10.1208/s12248-009-9110-7 Long, 2009, Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects, Nat Chem Biol, 5, 37, 10.1038/nchembio.129 Blankman, 2007, A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol, Chem Biol, 14, 1347, 10.1016/j.chembiol.2007.11.006 Villena, 2004, Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis, J Biol Chem, 279, 47066, 10.1074/jbc.M403855200 Rogalska, 1993, Stereoselective hydrolysis of triglycerides by animal and microbial lipases, Chirality, 5, 24, 10.1002/chir.530050106 Shewry, 2003, Tuber storage proteins, Ann Bot (Lond), 91, 755, 10.1093/aob/mcg084 Rydel, 2003, The crystal structure, mutagenesis, and activity studies reveal that patatin is a lipid acyl hydrolase with a Ser–Asp catalytic dyad, Biochemistry, 42, 6696, 10.1021/bi027156r Dessen, 1999, Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism, Cell, 97, 349, 10.1016/S0092-8674(00)80744-8 Notari, 2006, Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor, J Biol Chem, 281, 38022, 10.1074/jbc.M600353200 Chen, 2006, Assignment of the patatin-like phospholipase domain containing 2 gene (PNPLA2) to porcine chromosome 2p17 with radiation hybrids, Cytogenet Genome Res, 112, 342G, 10.1159/000089897 Saarela, 2008, The patatin-like lipase family in Gallus gallus, BMC Genomics, 9, 281, 10.1186/1471-2164-9-281 Gronke, 2005, Brummer lipase is an evolutionary conserved fat storage regulator in Drosophila, Cell Metab, 1, 323, 10.1016/j.cmet.2005.04.003 Eastmond, 2006, Sugar-dependent1 encodes a patatin domain triacylglycerol lipase that initiates storage oil breakdown in germinating Arabidopsis seeds, Plant Cell, 18, 665, 10.1105/tpc.105.040543 Kurat, 2006, Obese yeast: triglyceride lipolysis is functionally conserved from mammals to yeast, J Biol Chem, 281, 491, 10.1074/jbc.M508414200 Athenstaedt, 2005, Tgl4p and Tgl5p, two triacylglycerol lipases of the yeast Saccharomyces cerevisiae are localized to lipid particles, J Biol Chem, 280, 37301, 10.1074/jbc.M507261200 Kim, 2006, The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-alpha in 3T3–L1 adipocytes and is a target for transactivation by PPARgamma, Am J Physiol Endocrinol Metab, 291, E115, 10.1152/ajpendo.00317.2005 Lake, 2005, Expression, regulation, and triglyceride hydrolase activity of adiponutrin family members, J Lipid Res, 46, 2477, 10.1194/jlr.M500290-JLR200 Kershaw, 2006, Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin, Diabetes, 55, 148, 10.2337/diabetes.55.01.06.db05-0982 Duncan, 2010, Characterization of desnutrin functional domains: critical residues for triacylglycerol hydrolysis in cultured cells, J Lipid Res, 51, 309, 10.1194/jlr.M000729 Schweiger, 2008, The C-terminal region of human adipose triglyceride lipase affects enzyme activity and lipid droplet binding, J Biol Chem, 283, 17211, 10.1074/jbc.M710566200 Kobayashi, 2008, The lack of the C-terminal domain of adipose triglyceride lipase causes neutral lipid storage disease through impaired interactions with lipid droplets, J Clin Endocrinol Metab, 93, 2877, 10.1210/jc.2007-2247 Vaughan, 1964, Hormone-sensitive lipase and monoglyceride lipase activities in adipose tissue, J Biol Chem, 239, 401, 10.1016/S0021-9258(18)51692-6 Bjorntorp, 1962, Lipolytic activity in rat epididymal fat pads, Am J Physiol, 203, 316, 10.1152/ajplegacy.1962.203.2.316 Hollenberg, 1961, The lipolytic response to corticotropin, Endocrinology, 68, 589, 10.1210/endo-68-4-589 MA, 1964, Activation of an epinephrine-sensitive lipolytic activity from adipose tissue by adenosine 3′,5′-phosphate, J Biol Chem, 239, 392, 10.1016/S0021-9258(18)51690-2 Yeaman, 1994, The multifunctional role of hormone-sensitive lipase in lipid metabolism, Adv Enzyme Regul, 34, 355, 10.1016/0065-2571(94)90022-1 Yeaman, 1990, Hormone-sensitive lipase – a multipurpose enzyme in lipid metabolism, Biochim Biophys Acta, 1052, 128, 10.1016/0167-4889(90)90067-N Kraemer, 1993, Detection of hormone-sensitive lipase in various tissues. I. Expression of an HSL/bacterial fusion protein and generation of anti-HSL antibodies, J Lipid Res, 34, 663, 10.1016/S0022-2275(20)39990-9 Kraemer, 1993, Detection of hormone-sensitive lipase in various tissues. II. Regulation in the rat testis by human chorionic gonadotropin, J Lipid Res, 34, 609, 10.1016/S0022-2275(20)39984-3 Holm, 1989, Human adipose tissue hormone-sensitive lipase: identification and comparison with other species, Biochim Biophys Acta, 1006, 193, 10.1016/0005-2760(89)90195-1 Tsujita, 1989, P-Nitrophenyl butyrate hydrolyzing activity of hormone-sensitive lipase from bovine adipose tissue, J Lipid Res, 30, 997, 10.1016/S0022-2275(20)38302-4 Anthonsen, 1997, Partial purification and identification of hormone-sensitive lipase from chicken adipose tissue, Biochem Biophys Res Commun, 236, 94, 10.1006/bbrc.1997.6923 Khoo, 1993, Expression of hormone-sensitive lipase mRNA in macrophages, J Lipid Res, 34, 1969, 10.1016/S0022-2275(20)35114-2 Sztalryd, 1994, Regulation of hormone-sensitive lipase during fasting, Am J Physiol, 266, E179 Langin, 1993, Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxella TA144, an antarctic bacterium, Proc Natl Acad Sci USA, 90, 4897, 10.1073/pnas.90.11.4897 Laurin, 2000, The hormone-sensitive lipase gene is transcribed from at least five alternative first exons in mouse adipose tissue, Mamm Genome, 11, 972, 10.1007/s003350010185 Osterlund, 1996, Domain-structure analysis of recombinant rat hormone-sensitive lipase, Biochem J, 319, 411, 10.1042/bj3190411 Shen, 1999, Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein, Proc Natl Acad Sci USA, 96, 5528, 10.1073/pnas.96.10.5528 Fu, 2006, Lipid metabolism mediated by adipocyte lipid binding protein (ALBP/aP2) gene expression in human THP-1 macrophages, Atherosclerosis, 188, 102, 10.1016/j.atherosclerosis.2005.10.041 Shen, 2000, Hormone-sensitive lipase functions as an oligomer, Biochemistry, 39, 2392, 10.1021/bi992283h Shen, 2001, Characterization of the functional interaction of adipocyte lipid-binding protein with hormone-sensitive lipase, J Biol Chem, 276, 49443, 10.1074/jbc.M104095200 Contreras, 1996, Hormone-sensitive lipase is structurally related to acetylcholinesterase, bile salt-stimulated lipase, and several fungal lipases. Building of a three-dimensional model for the catalytic domain of hormone-sensitive lipase, J Biol Chem, 271, 31426, 10.1074/jbc.271.49.31426 Osterlund, 1997, Identification of essential aspartic acid and histidine residues of hormone-sensitive lipase: apparent residues of the catalytic triad, FEBS Lett, 403, 259, 10.1016/S0014-5793(97)00063-X Anthonsen, 1998, Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro, J Biol Chem, 273, 215, 10.1074/jbc.273.1.215 Greenberg, 2001, Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal-regulated kinase pathway, J Biol Chem, 276, 45456, 10.1074/jbc.M104436200 Shen, 1998, Mutational analysis of structural features of rat hormone-sensitive lipase, Biochemistry, 37, 8973, 10.1021/bi980545u Hemila, 1994, Hormone-sensitive lipase is closely related to several bacterial proteins, and distantly related to acetylcholinesterase and lipoprotein lipase: identification of a superfamily of esterases and lipases, Biochim Biophys Acta, 1210, 249, 10.1016/0005-2760(94)90129-5 Tornqvist, 1976, Purification and some properties of a monoacylglycerol-hydrolyzing enzyme of rat adipose tissue, J Biol Chem, 251, 813, 10.1016/S0021-9258(17)33857-7 Bertrand, 2010, Structural basis for human monoglyceride lipase inhibition, J Mol Biol, 396, 663, 10.1016/j.jmb.2009.11.060 Labar, 2010, Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling, Chembiochem, 11, 218, 10.1002/cbic.200900621 Dinh, 2002, Brain monoglyceride lipase participating in endocannabinoid inactivation, Proc Natl Acad Sci USA, 99, 10819, 10.1073/pnas.152334899 Schweiger, 2006, Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism, J Biol Chem, 281, 40236, 10.1074/jbc.M608048200 Kienesberger, 2009, Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions, J Lipid Res, 50, S63, 10.1194/jlr.R800082-JLR200 Romeo, 2010, Unravelling the pathogenesis of fatty liver disease: patatin-like phospholipase domain-containing 3 protein, Curr Opin Lipidol, 21, 247, 10.1097/MOL.0b013e328338ca61 Hoekstra, 2010, The expression level of non-alcoholic fatty liver disease-related gene PNPLA3 in hepatocytes is highly influenced by hepatic lipid status, J Hepatol, 52, 244, 10.1016/j.jhep.2009.11.004 He, 2010, A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis, J Biol Chem, 285, 6706, 10.1074/jbc.M109.064501 Huang, 2010, A feed-forward loop amplifies nutritional regulation of PNPLA3, Proc Natl Acad Sci USA, 107, 7892, 10.1073/pnas.1003585107 Chen, 2010, Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease, Hepatology, 52, 1134, 10.1002/hep.23812 Gao, 2007, A comparative study of human GS2, its paralogues, and its rat orthologue, Biochem Biophys Res Commun, 360, 501, 10.1016/j.bbrc.2007.06.089 Gao, 2005, Identification of a novel keratinocyte retinyl ester hydrolase as a transacylase and lipase, J Invest Dermatol, 124, 1259, 10.1111/j.0022-202X.2005.23761.x Lee, 1994, Isolation of a new gene GS2 (DXS1283E) from a CpG island between STS and KAL1 on Xp22.3, Genomics, 22, 372, 10.1006/geno.1994.1397 Shapiro, 1989, Molecular studies of deletions at the human steroid sulfatase locus, Proc Natl Acad Sci USA, 86, 8477, 10.1073/pnas.86.21.8477 Okazaki, 2006, Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis, Diabetes, 55, 2091, 10.2337/db05-0585 Gilham, 2005, Triacylglycerol hydrolase is localized to the endoplasmic reticulum by an unusual retrieval sequence where it participates in VLDL assembly without utilizing VLDL lipids as substrates, Mol Biol Cell, 16, 984, 10.1091/mbc.E04-03-0224 Gruber, 2010, The N-terminal region of comparative gene identification-58 (CGI-58) is important for lipid droplet binding and activation of adipose triglyceride lipase, J Biol Chem, 285, 12289, 10.1074/jbc.M109.064469 Granneman, 2009, Perilipin controls lipolysis by regulating the interactions of AB-hydrolase containing 5 (Abhd5) and adipose triglyceride lipase (Atgl), J Biol Chem, 284, 34538, 10.1074/jbc.M109.068478 Yang, 2010, Identification of a novel splicing isoform of murine CGI-58, FEBS Lett, 584, 903, 10.1016/j.febslet.2009.12.058 Ollis, 1992, The alpha/beta hydrolase fold, Protein Eng, 5, 197, 10.1093/protein/5.3.197 Granneman, 2007, Analysis of lipolytic protein trafficking and interactions in adipocytes, J Biol Chem, 282, 5726, 10.1074/jbc.M610580200 Ghosh, 2008, CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid, J Biol Chem, 283, 24525, 10.1074/jbc.M801783200 Montero-Moran, 2010, CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase, J Lipid Res, 51, 709, 10.1194/jlr.M001917 Russell, 1991, A human putative lymphocyte G0/G1 switch gene containing a CpG-rich island encodes a small basic protein with the potential to be phosphorylated, DNA Cell Biol, 10, 581, 10.1089/dna.1991.10.581 Zandbergen, 2005, The G0/G1 switch gene 2 is a novel PPAR target gene, Biochem J, 392, 313, 10.1042/BJ20050636 Welch, 2009, Identification of a protein, G0S2, that lacks Bcl-2 homology domains and interacts with and antagonizes Bcl-2, Cancer Res, 69, 6782, 10.1158/0008-5472.CAN-09-0128 Kurat, 2009, Cdk1/Cdc28-dependent activation of the major triacylglycerol lipase Tgl4 in yeast links lipolysis to cell-cycle progression, Mol Cell, 33, 53, 10.1016/j.molcel.2008.12.019 Haemmerle, 2002, Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle, J Biol Chem, 277, 12946, 10.1074/jbc.M108640200 Mulder, 2003, Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact, J Biol Chem, 278, 36380, 10.1074/jbc.M213032200 Bickel, 2009, PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores, Biochim Biophys Acta, 1791, 419, 10.1016/j.bbalip.2009.04.002 Yamaguchi, 2006, MLDP, a novel PAT family protein localized to lipid droplets and enriched in the heart, is regulated by peroxisome proliferator-activated receptor alpha, J Biol Chem, 281, 14232, 10.1074/jbc.M601682200 Wolins, 2006, OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization, Diabetes, 55, 3418, 10.2337/db06-0399 Dalen, 2007, LSDP5 is a PAT protein specifically expressed in fatty acid oxidizing tissues, Biochim Biophys Acta, 1771, 210, 10.1016/j.bbalip.2006.11.011 Subramanian, 2004, Perilipin A mediates the reversible binding of CGI-58 to lipid droplets in 3T3-L1 adipocytes, J Biol Chem, 279, 42062, 10.1074/jbc.M407462200 Listenberger, 2007, Adipocyte differentiation-related protein reduces the lipid droplet association of adipose triglyceride lipase and slows triacylglycerol turnover, J Lipid Res, 48, 2751, 10.1194/jlr.M700359-JLR200 Bell, 2008, Consequences of lipid droplet coat protein downregulation in liver cells: abnormal lipid droplet metabolism and induction of insulin resistance, Diabetes, 57, 2037, 10.2337/db07-1383 Tansey, 2001, Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity, Proc Natl Acad Sci USA, 98, 6494, 10.1073/pnas.101042998 Wolins, 2003, Adipocyte protein S3-12 coats nascent lipid droplets, J Biol Chem, 278, 37713, 10.1074/jbc.M304025200 Wolins, 2005, S3-12, adipophilin, and TIP47 package lipid in adipocytes, J Biol Chem, 280, 19146, 10.1074/jbc.M500978200 Granneman, 2009, Functional interactions between Mldp (LSDP5) and Abhd5 in the control of intracellular lipid accumulation, J Biol Chem, 284, 3049, 10.1074/jbc.M808251200 Puri, 2007, Fat-specific protein 27, a novel lipid droplet protein that enhances triglyceride storage, J Biol Chem, 282, 34213, 10.1074/jbc.M707404200 Keller, 2008, Fat-specific protein 27 regulates storage of triacylglycerol, J Biol Chem, 283, 14355, 10.1074/jbc.M708323200 Guo, 2008, Functional genomic screen reveals genes involved in lipid-droplet formation and utilization, Nature, 453, 657, 10.1038/nature06928 Beller, 2008, COPI complex is a regulator of lipid homeostasis, PLoS Biol, 6, e292, 10.1371/journal.pbio.0060292 Soni, 2009, Coatomer-dependent protein delivery to lipid droplets, J Cell Sci, 122, 1834, 10.1242/jcs.045849 Bartz, 2007, Dynamic activity of lipid droplets: protein phosphorylation and GTP-mediated protein translocation, J Proteome Res, 6, 3256, 10.1021/pr070158j Narbonne, 2009, Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival, Nature, 457, 210, 10.1038/nature07536 Kershaw, 2007, PPARgamma regulates adipose triglyceride lipase in adipocytes in vitro and in vivo, Am J Physiol Endocrinol Metab, 293, E1736, 10.1152/ajpendo.00122.2007 Festuccia, 2006, PPARgamma agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control, Diabetologia, 49, 2427, 10.1007/s00125-006-0336-y Chakrabarti, 2009, FoxO1 controls insulin-dependent adipose triglyceride lipase (ATGL) expression and lipolysis in adipocytes, J Biol Chem, 284, 13296, 10.1074/jbc.C800241200 Liu, 2009, Regulation of adipose triglyceride lipase by rosiglitazone, Diabetes Obes Metab, 11, 131, 10.1111/j.1463-1326.2008.00916.x Jocken, 2007, Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state, J Clin Endocrinol Metab, 92, 2292, 10.1210/jc.2006-1318 Kralisch, 2005, Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes, Mol Cell Endocrinol, 240, 43, 10.1016/j.mce.2005.06.002 Chakrabarti, 2010, The mTOR complex 1 suppresses lipolysis, stimulates lipogenesis and promotes fat storage, Diabetes, 59, 775, 10.2337/db09-1602 Reidy, 2000, Leptin: an essential regulator of lipid metabolism, Comp Biochem Physiol A Mol Integr Physiol, 125, 285, 10.1016/S1095-6433(00)00159-8 Shen, 2007, In vivo effects of leptin on autonomic nerve activity and lipolysis in rats, Neurosci Lett, 416, 193, 10.1016/j.neulet.2007.02.003 Krempler, 2000, Leptin, peroxisome proliferator-activated receptor-gamma, and CCAAT/enhancer binding protein-alpha mRNA expression in adipose tissue of humans and their relation to cardiovascular risk factors, Arterioscler Thromb Vasc Biol, 20, 443, 10.1161/01.ATV.20.2.443 Li, 2010, Regulation of ATGL expression mediated by leptin in vitro in porcine adipocyte lipolysis, Mol Cell Biochem, 333, 121, 10.1007/s11010-009-0212-4 Kraemer, 2002, Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis, J Lipid Res, 43, 1585, 10.1194/jlr.R200009-JLR200 Watt, 2004, Regulation and role of hormone-sensitive lipase activity in human skeletal muscle, Proc Nutr Soc, 63, 315, 10.1079/PNS2004360 Donsmark, 2004, Regulation and role of hormone-sensitive lipase in rat skeletal muscle, Proc Nutr Soc, 63, 309, 10.1079/PNS2004359 Langfort, 2003, Hormone-sensitive lipase in skeletal muscle: regulatory mechanisms, Acta Physiol Scand, 178, 397, 10.1046/j.1365-201X.2003.01155.x Krintel, 2008, Ser649 and Ser650 are the major determinants of protein kinase A-mediated activation of human hormone-sensitive lipase against lipid substrates, PLoS One, 3, e3756, 10.1371/journal.pone.0003756 Olsson, 1986, Phosphorylation of the basal site of hormone-sensitive lipase by glycogen synthase kinase-4, FEBS Lett, 209, 175, 10.1016/0014-5793(86)81106-1 Garton, 1989, Phosphorylation of bovine hormone-sensitive lipase by the AMP-activated protein kinase. A possible antilipolytic mechanism, Eur J Biochem, 179, 249, 10.1111/j.1432-1033.1989.tb14548.x Martinez-Botas, 2000, Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice, Nat Genet, 26, 474, 10.1038/82630 Tansey, 2003, Functional studies on native and mutated forms of perilipins. A role in protein kinase A-mediated lipolysis of triacylglycerols, J Biol Chem, 278, 8401, 10.1074/jbc.M211005200 Sztalryd, 2003, Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation, J Cell Biol, 161, 1093, 10.1083/jcb.200210169 Miyoshi, 2007, Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes, J Biol Chem, 282, 996, 10.1074/jbc.M605770200 Wang, 2009, Activation of hormone-sensitive lipase requires two steps, protein phosphorylation and binding to the PAT-1 domain of lipid droplet coat proteins, J Biol Chem, 284, 32116, 10.1074/jbc.M109.006726 Shen, 2009, Functional interaction of hormone-sensitive lipase and perilipin in lipolysis, J Lipid Res, 50, 2306, 10.1194/jlr.M900176-JLR200 Kiens, 2006, Skeletal muscle lipid metabolism in exercise and insulin resistance, Physiol Rev, 86, 205, 10.1152/physrev.00023.2004 Donsmark, 2005, Hormone-sensitive lipase as mediator of lipolysis in contracting skeletal muscle, Exerc Sport Sci Rev, 33, 127, 10.1097/00003677-200507000-00005 Buchebner, 2010, Cholesteryl ester hydrolase activity is abolished in HSL−/− macrophages but unchanged in macrophages lacking KIAA1363, J Lipid Res, 51, 2896, 10.1194/jlr.M004259 Hansson, 2006, Inflammatory response in white adipose tissue in the non-obese hormone-sensitive lipase null mouse model, J Proteome Res, 5, 1701, 10.1021/pr060101h Kraemer, 2006, Hormone-sensitive lipase knockouts, Nutr Metab (Lond), 3, 12, 10.1186/1743-7075-3-12 Yeaman, 2004, Hormone-sensitive lipase – new roles for an old enzyme, Biochem J, 379, 11, 10.1042/bj20031811 Johnson, 2000, Hormone sensitive lipase mRNA in both monocyte and macrophage forms of the human THP-1 cell line, Comp Biochem Physiol B Biochem Mol Biol, 126, 543, 10.1016/S0305-0491(00)00220-0 Fredrikson, 1986, Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol, Biochim Biophys Acta, 876, 288, 10.1016/0005-2760(86)90286-9 Schoiswohl, 2010, Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids, J Lipid Res, 51, 490, 10.1194/jlr.M001073 Olivecrona, 2010, The crucial role of ATGL for energy supply of muscles, J Lipid Res, 51, 449, 10.1194/jlr.E004770 Huijsman, 2009, Adipose triacylglycerol lipase deletion alters whole body energy metabolism and impairs exercise performance in mice, Am J Physiol Endocrinol Metab, 297, E505, 10.1152/ajpendo.00190.2009 Ahmadian, 2009, Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity, Diabetes, 58, 855, 10.2337/db08-1644 Randle, 1963, The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus, Lancet, 1, 785, 10.1016/S0140-6736(63)91500-9 Hue, 2009, The Randle cycle revisited: a new head for an old hat, Am J Physiol Endocrinol Metab, 297, E578, 10.1152/ajpendo.00093.2009 Schaffer, 2003, Lipotoxicity: when tissues overeat, Curr Opin Lipidol, 14, 281, 10.1097/00041433-200306000-00008 Kienesberger, 2009, Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling, J Biol Chem, 284, 30218, 10.1074/jbc.M109.047787 Peyot, 2009, Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated insulin secretion, J Biol Chem, 284, 16848, 10.1074/jbc.M109.006650 Tang, 1997, A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs, J Biol Chem, 272, 8567, 10.1074/jbc.272.13.8567 Yang, 2005, Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes, Nature, 436, 356, 10.1038/nature03711 Jourdan, 2009, Impact of type 1 diabetes and insulin treatment on plasma levels and fractional synthesis rate of retinol-binding protein 4, J Clin Endocrinol Metab, 94, 5125, 10.1210/jc.2009-1331 Goodman, 2009, The relationship of retinol binding protein 4 to changes in insulin resistance and cardiometabolic risk in overweight black adolescents, J Pediatr, 154, 67, 10.1016/j.jpeds.2008.07.018 Krzyzanowska, 2008, Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes, Diabetologia, 51, 1115, 10.1007/s00125-008-1009-9 Hammarstedt, 2008, High circulating levels of RBP4 and mRNA levels of aP2, PGC-1alpha and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naive type 2 diabetic subjects, J Intern Med, 263, 440, 10.1111/j.1365-2796.2007.01914.x Kovacs, 2007, Effects of genetic variation in the human retinol binding protein-4 gene (RBP4) on insulin resistance and fat depot-specific mRNA expression, Diabetes, 56, 3095, 10.2337/db06-1647 Balagopal, 2007, Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation, J Clin Endocrinol Metab, 92, 1971, 10.1210/jc.2006-2712 Graham, 2006, Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects, N Engl J Med, 354, 2552, 10.1056/NEJMoa054862 Langin, 2005, Adipocyte lipases and defect of lipolysis in human obesity, Diabetes, 54, 3190, 10.2337/diabetes.54.11.3190 Bezaire, 2009, Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes, J Biol Chem, 284, 18282, 10.1074/jbc.M109.008631 Chanarin, 1975, Neutral-lipid storage disease: a new disorder of lipid metabolism, Br Med J, 1, 553, 10.1136/bmj.1.5957.553 Igal, 1997, Neutral lipid storage disease with fatty liver and cholestasis, J Pediatr Gastroenterol Nutr, 25, 541, 10.1097/00005176-199711000-00011 Radom, 1987, Metabolism of neutral lipids in cultured fibroblasts from multisystemic (or type 3) lipid storage myopathy, Eur J Biochem, 164, 703, 10.1111/j.1432-1033.1987.tb11183.x Radom, 1990, Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein-Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects, Biochem J, 269, 107, 10.1042/bj2690107 Hilaire, 1995, The turnover of cytoplasmic triacylglycerols in human fibroblasts involves two separate acyl chain length-dependent degradation pathways, J Biol Chem, 270, 27027, 10.1074/jbc.270.45.27027 Hilaire, 1994, Cellular uptake and catabolism of high-density-lipoprotein triacylglycerols in human cultured fibroblasts: degradation block in neutral lipid storage disease, Biochem J, 297, 467, 10.1042/bj2970467 Hilaire, 1993, Cytoplasmic triacylglycerols and cholesteryl esters are degraded in two separate catabolic pools in cultured human fibroblasts, FEBS Lett, 328, 230, 10.1016/0014-5793(93)80933-L Igal, 1996, Acylglycerol recycling from triacylglycerol to phospholipid, not lipase activity, is defective in neutral lipid storage disease fibroblasts, J Biol Chem, 271, 16644, 10.1074/jbc.271.28.16644 Igal, 1998, Neutral lipid storage disease: a genetic disorder with abnormalities in the regulation of phospholipid metabolism, J Lipid Res, 39, 31, 10.1016/S0022-2275(20)34200-0 Williams, 1988, Neutral lipid storage disease with ichthyosis: lipid content and metabolism of fibroblasts, J Inherit Metab Dis, 11, 131, 10.1007/BF01799862 Williams, 1991, Neutral lipid storage disease: a possible functional defect in phospholipid-linked triacylglycerol metabolism, Biochim Biophys Acta, 1096, 162, 10.1016/0925-4439(91)90055-E Bergman, 1993, Enhanced low-density lipoprotein degradation and cholesterol synthesis in monocyte-derived macrophages of patients with adult xanthogranulomatosis, J Invest Dermatol, 101, 880, 10.1111/1523-1747.ep12371711 Lefevre, 2001, Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome, Am J Hum Genet, 69, 1002, 10.1086/324121 Akiyama, 2007, Novel duplication mutation in the patatin domain of adipose triglyceride lipase (PNPLA2) in neutral lipid storage disease with severe myopathy, Muscle Nerve, 36, 856, 10.1002/mus.20869 Radner, 2010, Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58), J Biol Chem, 285, 7300, 10.1074/jbc.M109.081877 Jiang, 2010, PPARdelta activation promotes stratum corneum formation and epidermal permeability barrier development during late gestation, J Invest Dermatol, 130, 511, 10.1038/jid.2009.245 Jiang, 2009, Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor delta in human keratinocytes, J Biol Chem, 284, 18942, 10.1074/jbc.M109.006973 Demerjian, 2009, Activators of PPARs and LXR decrease the adverse effects of exogenous glucocorticoids on the epidermis, Exp Dermatol, 18, 643, 10.1111/j.1600-0625.2009.00841.x Schmuth, 2008, Thematic review series: skin lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology, J Lipid Res, 49, 499, 10.1194/jlr.R800001-JLR200 Man, 2008, Deficiency of PPARbeta/delta in the epidermis results in defective cutaneous permeability barrier homeostasis and increased inflammation, J Invest Dermatol, 128, 370, 10.1038/sj.jid.5701026 Coderch, 2003, Ceramides and skin function, Am J Clin Dermatol, 4, 107, 10.2165/00128071-200304020-00004 Mizutani, 2009, Ceramide biosynthesis in keratinocyte and its role in skin function, Biochimie, 91, 784, 10.1016/j.biochi.2009.04.001 Elias, 2008, Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism, J Lipid Res, 49, 697, 10.1194/jlr.R800002-JLR200 Demerjian, 2006, Barrier dysfunction and pathogenesis of neutral lipid storage disease with ichthyosis (Chanarin-Dorfman syndrome), J Invest Dermatol, 126, 2032, 10.1038/sj.jid.5700332 Akiyama, 2003, Truncation of CGI-58 protein causes malformation of lamellar granules resulting in ichthyosis in Dorfman-Chanarin syndrome, J Invest Dermatol, 121, 1029, 10.1046/j.1523-1747.2003.12520.x Elias, 1985, Neutral lipid storage disease with ichthyosis. Defective lamellar body contents and intracellular dispersion, Arch Dermatol, 121, 1000, 10.1001/archderm.1985.01660080054014 Yamaguchi, 2007, CGI-58 facilitates lipolysis on lipid droplets but is not involved in the vesiculation of lipid droplets caused by hormonal stimulation, J Lipid Res, 48, 1078, 10.1194/jlr.M600493-JLR200 Notredame, 2000, T-Coffee: a novel method for fast and accurate multiple sequence alignment, J Mol Biol, 302, 205, 10.1006/jmbi.2000.4042 Clamp, 2004, The Jalview Java alignment editor, Bioinformatics, 20, 426, 10.1093/bioinformatics/btg430 Kiefer, 2009, The SWISS-MODEL repository and associated resources, Nucleic Acids Res, 37, D387, 10.1093/nar/gkn750 Zou, 2000, Structure of Aspergillus niger epoxide hydrolase at 1.8 A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases, Structure, 8, 111, 10.1016/S0969-2126(00)00087-3