Lipolysis and lipid mobilization in human adipose tissue

Progress in Lipid Research - Tập 48 - Trang 275-297 - 2009
Max Lafontan1,2, Dominique Langin1,2,3
1Inserm U858, Institut de Médecine Moléculaire de Rangueil, IFR150-BMT, BP84225, F-31432 Toulouse Cedex 4, France
2Université Paul Sabatier, F-31062 Toulouse Cedex 9, France
3CHU de Toulouse, F-31432 Toulouse, France

Tài liệu tham khảo

Bouchard, 1993, Genetic and nongenetic determinants of regional fat distribution, Endocr Rev, 14, 72, 10.1210/edrv-14-1-72 Frayn, 2002, Adipose tissue as a buffer for daily lipid flux, Diabetologia, 45, 1201, 10.1007/s00125-002-0873-y Ioka, 2003, Expression cloning and characterization of a novel glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein, GPI-HBP1, J Biol Chem, 278, 7344, 10.1074/jbc.M211932200 Beigneux, 2007, Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons, Cell Metab, 5, 279, 10.1016/j.cmet.2007.02.002 Schaffer, 2002, Fatty acid transport: the roads taken, Am J Physiol Endocrinol Metab, 282, E239, 10.1152/ajpendo.00462.2001 Hamilton, 2002, Mechanism of cellular uptake of long-chain fatty acids: do we need cellular proteins?, Mol Cell Biochem, 239, 17, 10.1023/A:1020542220599 Kamp, 2006, How fatty acids of different chain length enter and leave cells by free diffusion, Prostaglandins Leukot Essent Fatty Acids, 75, 149, 10.1016/j.plefa.2006.05.003 Frohnert, 2000, Regulation of fatty acid transporters in mammalian cells, Prog Lipid Res, 39, 83, 10.1016/S0163-7827(99)00018-1 Hajri, 2002, Fatty acid transport across membranes: relevance to nutrition and metabolic pathology, Annu Rev Nutr, 22, 383, 10.1146/annurev.nutr.22.020402.130846 Pohl, 2004, Role of FATP in parenchymal cell fatty acid uptake, Biochim Biophys Acta, 1686, 1, 10.1016/j.bbalip.2004.06.004 Bartness, 2007, Thematic review series: adipocyte biology. Sympathetic and sensory innervation of white adipose tissue, J Lipid Res, 48, 1655, 10.1194/jlr.R700006-JLR200 Romijn, 2005, Sympathetic and parasympathetic innervation of adipose tissue: metabolic implications, Curr Opin Clin Nutr Metab Care, 8, 440, 10.1097/01.mco.0000172586.09762.55 Valet, 2002, Understanding adipose tissue development from transgenic animal models, J Lipid Res, 43, 835, 10.1016/S0022-2275(20)30458-2 Rodbell, 1964, Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis, J Biol Chem, 239, 375, 10.1016/S0021-9258(18)51687-2 Hauner, 1989, Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium, J Clin Invest, 84, 1663, 10.1172/JCI114345 Sengenes, 2005, Preadipocytes in the human subcutaneous adipose tissue display distinct features from the adult mesenchymal and hematopoietic stem cells, J Cell Physiol, 205, 114, 10.1002/jcp.20381 Lonnroth, 1987, A microdialysis method allowing characterization of intercellular water space in humans, Am J Physiol, 253, E228 Arner, 1988, Control of lipolysis and its relevance to development of obesity in man, Diabetes Metab Rev, 4, 507, 10.1002/dmr.5610040507 Bolinder, 1992, Microdialysis measurement of the absolute glucose concentration in subcutaneous adipose tissue allowing glucose monitoring in diabetic patients, Diabetologia, 35, 1177, 10.1007/BF00401374 Galitzky, 1993, Role of vascular alpha-2 adrenoceptors in regulating lipid mobilization from human adipose tissue, J Clin Invest, 91, 1997, 10.1172/JCI116421 Barbe, 1996, In situ assessment of the role of the β1-, β2- and β3-adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue, Br J Pharmacol, 117, 907, 10.1111/j.1476-5381.1996.tb15279.x Lafontan, 1996, Application of in situ microdialysis to measure metabolic and vascular responses in adipose tissue, Trends Pharmacol Sci, 17, 309, 10.1016/0165-6147(96)40002-5 Schaupp, 1999, Direct access to interstitial fluid in adipose tissue in humans by use of open-flow microperfusion, Am J Physiol, 276, E401 Zierler, 1961, Theory of the use of arteriovenous concentration differences for measuring metabolism in steady and non-steady states, J Clin Invest, 40, 2111, 10.1172/JCI104437 Frayn, 1989, Metabolic characteristics of human adipose tissue in vivo, Clin Sci (Lond), 76, 509, 10.1042/cs0760509 Frayn, 1993, Subcutaneous adipose tissue metabolism studied by local cartheterization, Int J Obes, 17, S18 Coppack, 1994, In vivo regulation of lipolysis in humans, J Lipid Res, 35, 177, 10.1016/S0022-2275(20)41207-6 Lange, 2002, Lipolysis in human adipose tissue during exercise: comparison of microdialysis and a-v measurements, J Appl Physiol, 92, 1310, 10.1152/japplphysiol.00690.2001 Mittendorfer, 2003, What does the measurement of whole-body fatty acid rate of appearance in plasma by using a fatty acid tracer really mean?, Diabetes, 52, 1641, 10.2337/diabetes.52.7.1641 Votruba, 2007, Regional fat deposition as a factor in FFA metabolism, Annu Rev Nutr, 27, 149, 10.1146/annurev.nutr.27.061406.093754 Mutch, 2006, Identifying regulatory hubs in obesity with nutrigenomics, Curr Opin Endocrinol Diabetes, 13, 431, 10.1097/01.med.0000244224.76033.06 Mutch, 2007, Adipose gene expression prior to weight loss can differentiate, weakly predict dietary responders, PLoS ONE, 2, e1344, 10.1371/journal.pone.0001344 Capel, 2008, Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women, J Clin Endocrinol Metab, 93, 4315, 10.1210/jc.2008-0814 Clément, 2004, Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects, FASEB J, 18, 1657, 10.1096/fj.04-2204com Henegar, 2008, Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity, Genome Biol, 9, R14, 10.1186/gb-2008-9-1-r14 Brasaemle, 2004, Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes, J Biol Chem, 279, 46835, 10.1074/jbc.M409340200 Londos, 1999, On the control of lipolysis in adipocytes, Ann N Y Acad Sci, 892, 155, 10.1111/j.1749-6632.1999.tb07794.x Brasaemle, 2008, Perilipin A and the control of triacylglycerol metabolism, Mol Cell Biochem Brasaemle, 2007, Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis, J Lipid Res, 48, 2547, 10.1194/jlr.R700014-JLR200 Ducharme, 2008, Lipid droplets in lipogenesis and lipolysis, Endocrinology, 149, 942, 10.1210/en.2007-1713 Greenberg, 1993, Isolation of cDNAs for perilipins A and B: sequence and expression of lipid droplet-associated proteins of adipocytes, Proc Natl Acad Sci USA, 90, 12035, 10.1073/pnas.90.24.12035 Subramanian, 2004, Hydrophobic sequences target and anchor perilipin A to lipid droplets, J Lipid Res, 45, 1983, 10.1194/jlr.M400291-JLR200 Garcia, 2004, The amino and carboxyl termini of perilipin A facilitate the storage of triacylglycerols, J Biol Chem, 279, 8409, 10.1074/jbc.M311198200 Sengenes, 2003, Involvement of a cGMP-dependent pathway in the natriuretic peptide-mediated hormone-sensitive lipase phosphorylation in human adipocytes, J Biol Chem, 278, 48617, 10.1074/jbc.M303713200 Martinez-Botas, 2000, Absence of perilipin results in leanness and reverses obesity in Leprdb/db mice, Nat Genet, 26, 474, 10.1038/82630 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 Castro-Chavez, 2003, Coordinated upregulation of oxidative pathways and downregulation of lipid biosynthesis underlie obesity resistance in perilipin knockout mice: a microarray gene expression profile, Diabetes, 52, 2666, 10.2337/diabetes.52.11.2666 Kovsan, 2007, Regulation of adipocyte lipolysis by degradation of the perilipin protein: nelfinavir enhances lysosome-mediated perilipin proteolysis, J Biol Chem, 282, 21704, 10.1074/jbc.M702223200 Mottagui-Tabar, 2003, Evidence for an important role of perilipin in the regulation of human adipocyte lipolysis, Diabetologia, 46, 789, 10.1007/s00125-003-1112-x Beller, 2008, COPI complex is a regulator of lipid homeostasis, PLoS Biol, 6, e292, 10.1371/journal.pbio.0060292 Parton, 2007, The multiple faces of caveolae, Nat Rev Mol Cell Biol, 8, 185, 10.1038/nrm2122 Patel, 2008, Caveolae as organizers of pharmacologically relevant signal transduction molecules, Annu Rev Pharmacol Toxicol, 48, 359, 10.1146/annurev.pharmtox.48.121506.124841 Pilch, 2007, Cellular spelunking: exploring adipocyte caveolae, J Lipid Res, 48, 2103, 10.1194/jlr.R700009-JLR200 Cohen, 2004, Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation, Diabetes, 53, 1261, 10.2337/diabetes.53.5.1261 Razani, 1999, Regulation of cAMP-mediated signal transduction via interaction of caveolins with the catalytic subunit of protein kinase A, J Biol Chem, 274, 26353, 10.1074/jbc.274.37.26353 Razani, 2001, Two distinct caveolin-1 domains mediate the functional interaction of caveolin-1 with protein kinase A, Am J Physiol Cell Physiol, 281, C1241, 10.1152/ajpcell.2001.281.4.C1241 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 Syu, 1999, Lipotransin: a novel docking protein for hormone-sensitive lipase, Mol Cell, 4, 109, 10.1016/S1097-2765(00)80192-6 Matarese, 1988, Purification of murine adipocyte lipid-binding protein. Characterization as a fatty acid- and retinoic acid-binding protein, J Biol Chem, 263, 14544, 10.1016/S0021-9258(18)68254-7 Furuhashi, 2008, Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets, Nat Rev Drug Discov, 7, 489, 10.1038/nrd2589 LaLonde, 1994, The up-and-down beta-barrel proteins, FASEB J, 8, 1240, 10.1096/fasebj.8.15.8001736 Scheja, 1999, Altered insulin secretion associated with reduced lipolytic efficiency in aP2−/− mice, Diabetes, 48, 1987, 10.2337/diabetes.48.10.1987 Coe, 1999, Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels, J Lipid Res, 40, 967, 10.1016/S0022-2275(20)32133-7 Jenkins-Kruchten, 2003, Fatty acid-binding protein-hormone-sensitive lipase interaction. Fatty acid dependence on binding, J Biol Chem, 278, 47636, 10.1074/jbc.M307680200 Smith, 2007, Interaction of the adipocyte fatty acid-binding protein with the hormone-sensitive lipase: regulation by fatty acids and phosphorylation, J Biol Chem, 282, 32424, 10.1074/jbc.M703730200 Hotamisligil, 1996, Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein, Science, 274, 1377, 10.1126/science.274.5291.1377 Shaughnessy, 2000, Adipocyte metabolism in adipocyte fatty acid binding protein knockout mice (aP2−/−) after short-term high-fat feeding: functional compensation by the keratinocyte [correction of keritinocyte] fatty acid binding protein, Diabetes, 49, 904, 10.2337/diabetes.49.6.904 Hertzel, 2002, Increased lipolysis in transgenic animals overexpressing the epithelial fatty acid binding protein in adipose cells, J Lipid Res, 43, 2105, 10.1194/jlr.M200227-JLR200 Fisher, 2002, Fatty acid binding protein expression in different human adipose tissue depots in relation to rates of lipolysis and insulin concentration in obese individuals, Mol Cell Biochem, 239, 95, 10.1023/A:1020532823751 Furuhashi, 2008, Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice, J Clin Invest, 118, 2640 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 Zechner, 2009, Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores, J Lipid Res, 50, 3, 10.1194/jlr.R800031-JLR200 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 Yamaguchi, 2004, CGI-58 interacts with perilipin and is localized to lipid droplets. Possible involvement of CGI-58 mislocalization in Chanarin–Dorfman syndrome, J Biol Chem, 279, 30490, 10.1074/jbc.M403920200 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 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 Granneman, 2007, Analysis of lipolytic protein trafficking and interactions in adipocytes, J Biol Chem, 282, 5726, 10.1074/jbc.M610580200 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 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 Kishida, 2000, Aquaporin adipose, a putative glycerol channel in adipocytes, J Biol Chem, 275, 20896, 10.1074/jbc.M001119200 Hara-Chikuma, 2005, Progressive adipocyte hypertrophy in aquaporin-7-deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation, J Biol Chem, 280, 15493, 10.1074/jbc.C500028200 Hibuse, 2005, Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase, Proc Natl Acad Sci USA, 102, 10993, 10.1073/pnas.0503291102 Hibuse, 2006, Aquaporins and glycerol metabolism, Biochim Biophys Acta, 1758, 1004, 10.1016/j.bbamem.2006.01.008 Nordstrom, 2005, A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in adipocyte lipolysis and obesity, Diabetes, 54, 1726, 10.2337/diabetes.54.6.1726 Puri, 2008, Cidea is associated with lipid droplets and insulin sensitivity in humans, Proc Natl Acad Sci USA, 105, 7833, 10.1073/pnas.0802063105 Zhou, 2003, Cidea-deficient mice have lean phenotype and are resistant to obesity, Nat Genet, 35, 49, 10.1038/ng1225 Laurencikiene, 2008, Evidence for an important role of CIDEA in human cancer cachexia, Cancer Res, 68, 9247, 10.1158/0008-5472.CAN-08-1343 Magnusson, 2008, Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism, Metabolism, 57, 1307, 10.1016/j.metabol.2008.04.028 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 Wang, 2001, The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice, Obes Res, 9, 119, 10.1038/oby.2001.15 Haemmerle, 2002, Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle and testis, J Biol Chem, 477, 4806, 10.1074/jbc.M110355200 Strom, 2008, Attainment of brown adipocyte features in white adipocytes of hormone-sensitive lipase null mice, PLoS ONE, 3, e1793, 10.1371/journal.pone.0001793 Claus, 2005, Specific inhibition of hormone-sensitive lipase improves lipid profile while reducing plasma glucose, J Pharmacol Exp Ther, 315, 1396, 10.1124/jpet.105.086926 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 Holm, 2003, Molecular mechanisms regulating hormone-sensitive lipase and lipolysis, Biochem Soc Trans, 31, 1120, 10.1042/bst0311120 Haemmerle, 2003, Letting lipids go: hormone-sensitive lipase, Curr Opin Lipidol, 14, 289, 10.1097/00041433-200306000-00009 Yeaman, 2004, Hormone-sensitive lipase—new roles for an old enzyme, Biochem J, 379, 11, 10.1042/bj20031811 Grober, 1997, Characterization of the promoter of human adipocyte hormone-sensitive lipase, Biochem J, 328, 453, 10.1042/bj3280453 Grober, 2003, Hormone-sensitive lipase is a cholesterol esterase of the intestinal mucosa, J Biol Chem, 278, 6510, 10.1074/jbc.M208513200 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 Mairal, 2002, Characterization of a novel testicular form of human hormone-sensitive lipase, Biochem Biophys Res Commun, 291, 286, 10.1006/bbrc.2002.6427 Stenson Holst, 1996, Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase, Genomics, 35, 441, 10.1006/geno.1996.0383 Raclot, 1997, Selective release of human adipocyte fatty acids according to molecular structure, Biochem J, 324, 911, 10.1042/bj3240911 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 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 Sullivan, 1994, A cell-permeable activator of AMP-activated protein kinase, FEBS Lett, 353, 33, 10.1016/0014-5793(94)01006-4 Daval, 2005, Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes, J Biol Chem, 280, 25250, 10.1074/jbc.M414222200 Anthony, 2009, Regulation of visceral and subcutaneous adipocyte lipolysis by acute AICAR-induced AMPK activation, Obesity, 10.1038/oby.2008.645 Yin, 2003, Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis in 3T3-L1 adipocytes, J Biol Chem, 278, 43074, 10.1074/jbc.M308484200 Gaidhu, 2008, Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL, J Lipid Res, 10.1194/jlr.M800480-JLR200 Holm, 2000, Molecular mechanisms regulating hormone-sensitive lipase and lipolysis, Annu Rev Nutr, 20, 365, 10.1146/annurev.nutr.20.1.365 Brasaemle, 2000, The lipolytic stimulation of 3T3-L1 adipocytes promotes the translocation of hormone-sensitive lipase to the surfaces of lipid storage droplets, Biochim Biophys Acta, 1483, 251, 10.1016/S1388-1981(99)00179-1 Egan, 1992, Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet, Proc Natl Acad Sci USA, 89, 8537, 10.1073/pnas.89.18.8537 Hirsch, 1984, Lipolytic stimulation modulates the subcellular distribution of hormone-sensitive lipase in 3T3-L1 cells, J Lipid Res, 25, 665, 10.1016/S0022-2275(20)37755-5 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 Marcinkiewicz, 2006, The phosphorylation of serine 492 of perilipin A directs lipid droplet fragmentation and dispersion, J Biol Chem, 281, 11901, 10.1074/jbc.M600171200 Zimmermann, 2004, Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase, Science, 306, 1383, 10.1126/science.1100747 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 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 Mairal, 2006, Human adipose triglyceride lipase (PNPLA2) is not regulated by obesity and exhibits low in vitro triglyceride hydrolase activity, Diabetologia, 49, 1629, 10.1007/s00125-006-0272-x Kershaw, 2006, Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin, Diabetes, 55, 148, 10.2337/diabetes.55.01.06.db05-0982 Haemmerle, 2006, Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase, Science, 312, 734, 10.1126/science.1123965 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 Bezaire V, Mairal A, Ribet C, Lefort C, Girousse A, Jocken J, et al. Contribution of hormone-sensitive lipase and adipose triglyceride lipase to lipolysis in human hMADS adipocytes. J. Biol. Chem. 2009. Available from <http://www.jbc.org/cgi/doi/10.1074/jbc.M109.008631>. 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 Ryden, 2007, Comparative studies of the role of hormone-sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis, Am J Physiol Endocrinol Metab, 292, E1847, 10.1152/ajpendo.00040.2007 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 Lake, 2005, Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members, J Lipid Res, 46, 2477, 10.1194/jlr.M500290-JLR200 Soni, 2004, Carboxylesterase 3 (EC 3.1.1.1) is a major adipocyte lipase, J Biol Chem, 279, 40683, 10.1074/jbc.M400541200 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 Raclot, 1995, Selective mobilization of adipose tissue fatty acids during energy depletion in the rat, J Lipid Res, 36, 2164, 10.1016/S0022-2275(20)39200-2 Halliwell, 1996, Release of individual fatty acids from human adipose tissue in vivo after an overnight fast, J Lipid Res, 37, 1842, 10.1016/S0022-2275(20)37549-0 Raclot, 1995, Selectivity of fatty acid mobilization: a general metabolic feature of adipose tissue, Am J Physiol, 269, R1060 Vassaux, 1992, Differential response of preadipocytes and adipocytes to prostacyclin and prostaglandin E2: physiological implications, Endocrinology, 131, 2393, 10.1210/en.131.5.2393 Raclot, 2001, A role for hormone-sensitive lipase in the selective mobilization of adipose tissue fatty acids, Biochim Biophys Acta, 1532, 88, 10.1016/S1388-1981(01)00119-6 Raclot, 2001, Fatty acid specificity of hormone-sensitive lipase and its implication in the selective hydrolysis of adipose tissue triacylglycerols, J Lipid Res, 42, 2049, 10.1016/S0022-2275(20)31534-0 Raclot, 2003, Selective mobilization of fatty acids from adipose tissue triacylglycerols, Prog Lipid Res, 42, 257, 10.1016/S0163-7827(02)00066-8 Cao, 2008, Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism, Cell, 134, 933, 10.1016/j.cell.2008.07.048 Plée-Gauthier, 1996, Inhibition of hormone-sensitive lipase gene expression by cAMP and phorbol esters in 3T3-F442A and BFC-1 adipocytes, Biochem J, 318, 1057, 10.1042/bj3181057 Raclot, 1998, Regulation of hormone-sensitive lipase expression by glucose in 3T3-F442A adipocytes, Biochem Biophys Res Commun, 245, 510, 10.1006/bbrc.1998.8469 Botion, 1999, Long-term regulation of lipolysis and hormone-sensitive lipase by insulin and glucose, Diabetes, 48, 1691, 10.2337/diabetes.48.9.1691 Smih, 2002, Transcriptional regulation of adipocyte hormone-sensitive lipase by glucose, Diabetes, 51, 293, 10.2337/diabetes.51.2.293 Laurell, 1997, Species-specific alternative splicing generates a catalytically inactive form of human hormone-sensitive lipase, Biochem J, 328, 137, 10.1042/bj3280137 Langin, 2005, Adipocyte lipases and defect of lipolysis in human obesity, Diabetes, 54, 3190, 10.2337/diabetes.54.11.3190 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 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 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 Lafontan, 1993, Fat cell adrenergic receptors and the control of white and brown fat cell function, J Lipid Res, 34, 1057, 10.1016/S0022-2275(20)37695-1 Bachman, 2002, BetaAR signaling required for diet-induced thermogenesis and obesity resistance, Science, 297, 843, 10.1126/science.1073160 Tavernier, 2005, Norepinephrine induces lipolysis in beta1/beta2/beta3-adrenoceptor knockout mice, Mol Pharmacol, 68, 793, 10.1124/mol.105.014670 Robidoux, 2004, Beta-adrenergic receptors and regulation of energy expenditure: a family affair, Annu Rev Pharmacol Toxicol, 44, 297, 10.1146/annurev.pharmtox.44.101802.121659 Robidoux, 2006, Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal growth factor receptor-dependent ERK1/2 activation, J Biol Chem, 281, 37794, 10.1074/jbc.M605572200 Mauriège, 1988, Human fat cell beta-adrenergic receptors: beta agonist-dependent lipolytic responses and characterization of beta-adrenergic binding sites on human fat cell membranes with highly selective beta1-antagonists, J Lipid Res, 29, 587, 10.1016/S0022-2275(20)38502-3 Tavernier, 1996, Expression of β3-adrenoceptors with low lipolytic action in human subcutaneous fat cells, J Lipid Res, 37, 87, 10.1016/S0022-2275(20)37638-0 Galitzky, 1997, Lipolytic effects of conventional β3-adrenoceptor agonists and of CGP 12177 in rat and human fat cells: preliminary pharmacological evidence for a putative β4-adrenoceptor, Br J Pharmacol, 122, 1244, 10.1038/sj.bjp.0701523 Konkar, 2000, Β1-adrenergic receptors mediate β3-adrenergic-independent effects of CGP 12177 in brown adipose tissue, Mol Pharmacol, 57, 252 Granneman, 2001, The putative beta4-adrenergic receptor is a novel state of the beta1-adrenergic receptor, Am J Physiol Endocrinol Metab, 280, E199, 10.1152/ajpendo.2001.280.2.E199 Schiffelers, 2000, In vivo β3-adrenergic stimulation of human thermogenesis and lipid utilization, Clin Pharmacol Therap, 67, 558, 10.1067/mcp.2000.106794 Lafontan, 1979, An extra-adrenal action of adrenocorticotrophin: physiological induction of lipolysis by secretion of adrenocorticotrophin in obese rabbits, J Endocrinol, 81, 281, 10.1677/joe.0.0810281 Boston, 1999, The role of melanocortins in adipocyte function, Ann N Y Acad Sci, 885, 75, 10.1111/j.1749-6632.1999.tb08666.x Sinha, 1976, On the lipolytic action of parathyroid hormone in man, Metabolism, 25, 251, 10.1016/0026-0495(76)90083-4 Taniguchi, 1987, Parathyroid hormone-induced lipolysis in human adipose tissue, J Lipid Res, 28, 490, 10.1016/S0022-2275(20)38677-6 Bousquet-Melou, 1995, Control of lipolysis in intra-abdominal fat cells of non-human primates: comparison with humans, J Lipid Res, 36, 451, 10.1016/S0022-2275(20)39879-5 Marcus, 1988, Regulation of lipolysis during the neonatal period. Importance of thyrotropin, J Clin Invest, 82, 1793, 10.1172/JCI113793 Janson, 1998, Presence of thyrotropin receptor in infant adipocytes, Pediatr Res, 43, 555, 10.1203/00006450-199804000-00020 Eriksson, 2009, Endothelin-1 stimulates human adipocyte lipolysis through the ET A receptor, Int J Obes (Lond), 33, 67, 10.1038/ijo.2008.212 Lafontan, 1995, Fat cell α2-adrenoceptors: the regulation of fat cell function and lipolysis, Endocr Rev, 16, 716 Polak, 2007, Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue, J Lipid Res, 48, 2236, 10.1194/jlr.M700253-JLR200 Kaartinen, 1991, Attenuated adenosine-sensitivity and decreased adenosine-receptor number in adipocyte plasma membranes in human obesity, Biochem J, 279, 17, 10.1042/bj2790017 Richelsen, 1988, Prostaglandin E2 action and binding in human adipocytes: effects of sex, age, and obesity, Metabolism, 37, 268, 10.1016/0026-0495(88)90107-2 Wang, 2006, Small-molecule compounds that modulate lipolysis in adipose tissue: targeting strategies and molecular classes, Chem Biol, 13, 1019, 10.1016/j.chembiol.2006.09.010 Lorenzen, 2001, Characterization of a G protein-coupled receptor for nicotinic acid, Mol Pharmacol, 59, 349, 10.1124/mol.59.2.349 Tunaru, 2003, PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect, Nat Med, 9, 352, 10.1038/nm824 Wise, 2004, The identification of ligands at orphan G-protein coupled receptors, Annu Rev Pharmacol Toxicol, 44, 43, 10.1146/annurev.pharmtox.44.101802.121419 Taggart, 2005, (d)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G, J Biol Chem, 280, 26649, 10.1074/jbc.C500213200 Cai, 2008, Role of GPR81 in lactate-mediated reduction of adipose lipolysis, Biochem Biophys Res Commun, 377, 987, 10.1016/j.bbrc.2008.10.088 Liu, 2009, Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81, J Biol Chem, 284, 2811, 10.1074/jbc.M806409200 Regard, 2008, Anatomical profiling of G protein-coupled receptor expression, Cell, 135, 561, 10.1016/j.cell.2008.08.040 Ge, 2008, Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids, Endocrinology, 149, 4519, 10.1210/en.2008-0059 Hirasawa, 2008, Free fatty acid receptors and drug discovery, Biol Pharm Bull, 31, 1847, 10.1248/bpb.31.1847 Valet, 1990, Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein, J Clin Invest, 85, 291, 10.1172/JCI114425 Serradeil-Le Gal, 2000, Characterization of NPY receptors controlling lipolysis and leptin secretion in human adipocytes, FEBS Lett, 475, 150, 10.1016/S0014-5793(00)01649-5 Turtzo, 2001, Cross-talk between sympathetic neurons and adipocytes in coculture, Proc Natl Acad Sci USA, 98, 12385, 10.1073/pnas.231478898 Castan, 1993, Distribution of PYY receptors in human fat cells: an antilipolytic system alongside the alpha 2-adrenergic system, Am J Physiol, 265, E74 Kos, 2009, DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue, Diabetes Obes Metab, 11, 285, 10.1111/j.1463-1326.2008.00909.x Kuo, 2008, Chronic stress, combined with a high-fat/high-sugar diet, shifts sympathetic signaling toward neuropeptide Y and leads to obesity and the metabolic syndrome, Ann N Y Acad Sci, 1148, 232, 10.1196/annals.1410.035 Kather, 1988, Purine accumulation in human fat cell suspensions, J Biol Chem, 263, 8803, 10.1016/S0021-9258(18)68377-2 Kather, 1990, Pathways of purine metabolism in human adipocytes: further evidence against a role of adenosine as an endogenous regulator of human fat cell function, J Clin Invest, 265, 96 Lönnroth, 1989, Microdialysis of intercellular adenosine concentration in subcutaneous adipose tissue in humans, Am J Physiol, 256, E250 Liang, 2002, Tonic activity of the rat adipocyte A1-adenosine receptor, Br J Pharmacol, 135, 1457, 10.1038/sj.bjp.0704586 Fain, 2004, Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans, Endocrinology, 145, 2273, 10.1210/en.2003-1336 Duncan, 2008, Identification and functional characterization of adipose-specific phospholipase A2 (AdPLA), J Biol Chem, 283, 25428, 10.1074/jbc.M804146200 Jaworski, 2009, AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency, Nat Med, 10, 20 Moxham, 1993, Gialpha2 mediates the inhibitory regulation of adenylyl cyclase in vivo: analysis in transgenic mice with Gialpha2 suppressed by inducible antisense RNA, Dev Genet, 14, 266, 10.1002/dvg.1020140404 Kather, 1979, Biphasic effects of prostaglandin E2 on the human fat cell adenylate cyclase, J Clin Invest, 64, 609, 10.1172/JCI109500 Sengenes, 2000, Natriuretic peptides: a new lipolytic pathway in human adipocytes, FASEB J, 14, 1345, 10.1096/fj.14.10.1345 Yu, 2008, Differences in the amount of lipolysis induced by atrial natriuretic peptide in small and large adipocytes, J Pept Sci, 14, 972, 10.1002/psc.1035 Strålfors, 1985, Phosphorylation of hormone-sensitive lipase by cyclic GMP-dependent protein kinase, FEBS Lett, 180, 280, 10.1016/0014-5793(85)81086-3 Moro, 2007, Phosphodiesterase-5A and neutral endopeptidase activities in human adipocytes do not control atrial natriuretic peptide-mediated lipolysis, Br J Pharmacol, 152, 1102, 10.1038/sj.bjp.0707485 Galitzky, 2001, The lipid mobilizing effect of atrial natriuretic peptide is unrelated to sympathetic nervous system activation or obesity in young men, J Lipid Res, 42, 536, 10.1016/S0022-2275(20)31162-7 Sengenes, 2002, Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women, Int J Obes Relat Metab Disord, 26, 24, 10.1038/sj.ijo.0801845 Birkenfeld, 2005, Lipid mobilization with physiological atrial natriuretic peptide concentrations in humans, J Clin Endocrinol Metab, 90, 3622, 10.1210/jc.2004-1953 Bolinder, 1987, Studies of acute effects of insulin-like growth factors I and II in human fat cells, J Clin Endocrinol Metab, 65, 732, 10.1210/jcem-65-4-732 Choi, 2006, Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice, J Clin Invest, 116, 3240, 10.1172/JCI24867 Saltiel, 2002, Insulin signaling pathways in time and space, Trends Cell Biol, 12, 65, 10.1016/S0962-8924(01)02207-3 Rondinone, 2000, Phosphorylation of PDE3B by phosphoinositol 3-kinase associated with the insulin receptor, J Biol Chem, 275, 10093, 10.1074/jbc.275.14.10093 Graves, 1996, Insulin, growth factors and cAMP. Antagonism in the signal transduction pathways, Trends Endocrinol Metab, 7, 43, 10.1016/1043-2760(95)00204-9 Tao, 2001, Insulin stimulates tyrosine phosphorylation and inactivation of protein-tyrosine phosphatase 1B in vivo, J Biol Chem, 276, 29520, 10.1074/jbc.M103721200 Zabolotny, 2008, Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo, J Biol Chem, 283, 14230, 10.1074/jbc.M800061200 Tao, 2001, Galpha(i2) enhances insulin signaling via suppression of protein-tyrosine phosphatase 1B, J Biol Chem, 276, 39705, 10.1074/jbc.M105216200 Moller, 2009, Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects, Endocr Rev, 10.1210/er.2008-0027 Harant, 1994, Response of fat cells to growth hormone (GH): effect of long term treatment with recombinant human GH in GH-deficient adults, J Clin Endocrinol Metab, 78, 1392, 10.1210/jc.78.6.1392 Doris, 1994, Growth hormone decreases the response to anti-lipolytic agonists and decreases the levels of Gi2 in rat adipocytes, Biochem J, 297, 41, 10.1042/bj2970041 Yip, 1999, Growth hormone and dexamethasone stimulate lipolysis and activate adenylyl cyclase in rat adipocytes by selectively shifting Gi alpha2 to lower density membrane fractions, Endocrinology, 140, 1219, 10.1210/en.140.3.1219 Jorgensen, 1991, Human growth hormone replacement therapy: pharmacological and clinical aspects, Endocr Rev, 12, 189, 10.1210/edrv-12-3-189 Boyle, 1992, Role of GH in regulating nocturnal rate of lipolysis and plasma mevalonate levels in normal and diabetic humans, Am J Physiol, 263, E168 Moller N, Gjedsted J, Gormsen L, Fuglsang J, Djurhuus C. Effects of growth hormone on lipid metabolism in humans. Growth Horm IGF Res 2003;13(Suppl. A):S18–21. Gravholt, 1999, Effects of a physiological GH pulse on interstitial glycerol in abdominal and femoral adipose tissue, Am J Physiol, 277, E848 Samra, 1999, Suppression of the nocturnal rise in growth hormone reduces subsequent lipolysis in subcutaneous adipose tissue, Eur J Clin Invest, 29, 1045, 10.1046/j.1365-2362.1999.00577.x Enevoldsen, 2007, Post-exercise abdominal, subcutaneous adipose tissue lipolysis in fasting subjects is inhibited by infusion of the somatostatin analogue octreotide, Clin Physiol Funct Imaging, 27, 320, 10.1111/j.1475-097X.2007.00754.x Divertie, 1991, Stimulation of lipolysis in humans by physiological hypercortisolemia, Diabetes, 40, 1228, 10.2337/diabetes.40.10.1228 Djurhuus, 2002, Effects of cortisol and regional interstitial glycerol levels in humans, J Clin Endocrinol Metab, 283, E172 Ottoson, 2000, Effects of cortisol and growth hormone on lipolysis in human adipose tissue, J Clin Endocrinol Metab, 85, 799, 10.1210/jc.85.2.799 Djuurhus, 2003, Additive effects of cortisol and growth hormone on regional and systemic lipolysis in humans, Am J Physiol Endocrinol Metab, 286, E488, 10.1152/ajpendo.00199.2003 Hefferman, 2000, Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism, Am J Physiol, 279, E501 Mohamed-Ali, 1997, Subcutaneous adipose tissue releases interleukin-6 but not tumor necrosis factor-α, in vivo, J Clin Endocrinol Metab, 82, 4196, 10.1210/jc.82.12.4196 Bastard, 2000, Elevated levels of interleukin-6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss, J Clin Endocrinol Metab, 85, 3338, 10.1210/jc.85.9.3338 Pedersen, 2008, Muscle as an endocrine organ: focus on muscle-derived interleukin-6, Physiol Rev, 88, 1379, 10.1152/physrev.90100.2007 Bastard, 2002, Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro, J Clin Endocrinol Metab, 87, 2084, 10.1210/jc.87.5.2084 Päth, 2001, Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function, J Clin Endocrinol Metab, 86, 2281, 10.1210/jc.86.5.2281 Lagathu, 2003, Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone, Biochem Biophys Res Commun, 311, 372, 10.1016/j.bbrc.2003.10.013 Rotter, 2003, Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-α, overexpressed in human fat cells from insulin resistant subjects, J Biol Chem, 278, 45777, 10.1074/jbc.M301977200 van Hall, 2003, Interleukin-6 stimulates lipolysis and fat oxidation in humans, J Clin Endocrinol Metab, 88, 3005, 10.1210/jc.2002-021687 Jensen, 2003, Cytokine regulation of lipolysis in humans?, J Clin Endocrinol Metab, 88, 3003, 10.1210/jc.2003-030703 Gustafson, 2006, Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes, J Biol Chem, 281, 9507, 10.1074/jbc.M512077200 Kawakami, 1987, Human recombinant TNF suppresses lipoprotein lipase activity and stimulates lipolysis in 3T3-L1 cells, J Biochem, 101, 331, 10.1093/oxfordjournals.jbchem.a121917 Hauner, 1995, Effects of tumor necrosis factor alpha (TNFα) on glucose transport and lipid metabolism of newly differentiated human fat cells in culture, Diabetologia, 38, 764, 10.1007/s001250050350 Langin, 2006, Importance of TNFalpha and neutral lipases in human adipose tissue lipolysis, Trends Endocrinol Metab, 17, 314, 10.1016/j.tem.2006.08.003 Sethi, 2000, Characterisation of receptor-specific TNFα functions in adipocyte cell lines lacking type 1 and 2 TNF receptors, FEBS Lett, 469, 77, 10.1016/S0014-5793(00)01250-3 Sethi, 1999, The role of TNFα in adipocyte metabolism, Cell Dev Biol, 10, 19, 10.1006/scdb.1998.0273 Ryden, 2002, Mapping of early signaling events in tumor necrosis factor-alpha-mediated lipolysis in human fat cells, J Biol Chem, 277, 1085, 10.1074/jbc.M109498200 Ryden, 2002, Mapping of early signalling events in TNF-α-mediated lipolysis in human fat cells, J Biol Chem, 277, 1085, 10.1074/jbc.M109498200 Engelman, 2000, Tumor necrosis factor alpha-mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-L1 adipocytes, Mol Endocrinol, 14, 1557, 10.1210/me.14.10.1557 Zhang, 2002, Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP, Diabetes, 51, 2929, 10.2337/diabetes.51.10.2929 Souza, 1998, Overexpression of perilipin A and B blocks the ability of tumor necrosis factor-α to increase lipolysis in 3T3-L1 adipocytes, J Biol Chem, 273, 24665, 10.1074/jbc.273.38.24665 Gasic, 1999, Tumor necrosis factor alpha stimulates lipolysis in adipocytes by decreasing Gi protein concentrations, J Biol Chem, 274, 6770, 10.1074/jbc.274.10.6770 Botion, 2001, Inhibition of proteasome activity blocks the ability of TNF alpha to down-regulate G(i) proteins and stimulate lipolysis, Endocrinology, 142, 5069, 10.1210/en.142.12.5069 Plomgaard, 2008, Tumor necrosis factor-alpha modulates human in vivo lipolysis, J Clin Endocrinol Metab, 93, 543, 10.1210/jc.2007-1761 Gaudiot, 1998, Modulation of white adipose tissue lipolysis by nitric oxide, J Biol Chem, 273, 13475, 10.1074/jbc.273.22.13475 Andersson, 1999, A nitric oxide-mediated mechanism regulates lipolysis in human adipose tissue in vivo, Br J Pharmacol, 126, 1639, 10.1038/sj.bjp.0702430 Siegrest-Kaiser, 1997, Direct effects of leptin on brown and white adipose tissues, J Clin Invest, 100, 2858, 10.1172/JCI119834 Frühbeck, 1997, In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin, Biochem Biophys Res Commun, 240, 590, 10.1006/bbrc.1997.7716 Elimam, 2002, In vitro effects of leptin on human adipocyte metabolism, Horm Res, 58, 88, 10.1159/000064659 Agustsson, 2007, Mechanism of increased lipolysis in cancer cachexia, Cancer Res, 67, 5531, 10.1158/0008-5472.CAN-06-4585 Tisdale, 1999, Wasting in cancer, J Nutr, 129, 243S, 10.1093/jn/129.1.243S Groundwater, 1990, Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients, Br J Cancer, 62, 816, 10.1038/bjc.1990.384 Bing, 2004, Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia, Proc Natl Acad Sci USA, 101, 2500, 10.1073/pnas.0308647100 Ryden, 2007, Fat loss in cachexia—is there a role for adipocyte lipolysis?, Clin Nutr, 26, 1, 10.1016/j.clnu.2006.09.009 Bing, 2008, Regulation of adipose tissue metabolism in cancer cachexia, Curr Opin Clin Nutr Metab Care, 11, 201, 10.1097/MCO.0b013e3282f948e2 Frayn, 2003, Integrative physiology of human adipose tissue, Int J Obes, 27, 875, 10.1038/sj.ijo.0802326 Lafontan, 2008, Control of lipolysis by natriuretic peptides and cyclic GMP, Trends Endocrinol Metab, 19, 130, 10.1016/j.tem.2007.11.006 Kissebah, 1994, Regional adiposity and morbidity, Physiol Rev, 74, 761, 10.1152/physrev.1994.74.4.761 Wajchenberg, 2000, Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome, Endocr Rev, 21, 697, 10.1210/er.21.6.697 Lafontan, 2003, Do regional differences in adipocyte biology provide new pathophysiological insights?, Trends Pharmacol Sci, 24, 276, 10.1016/S0165-6147(03)00132-9 Abate, 1995, Heterogeneity in adipose tissue metabolism: causes, implications and management of regional adiposity, Prog Lipid Res, 34, 53, 10.1016/0163-7827(94)00006-8 Arner, 1999, Catecholamine-induced lipolysis in obesity, Int J Obes, 23, 10, 10.1038/sj.ijo.0800789 Jensen, 1997, Lipolysis: contribution from regional fat, Annu Rev Nutr, 17, 127, 10.1146/annurev.nutr.17.1.127 Leibel, 1989, Physiologic basis for the control of body fat distribution in humans, Annu Rev Nutr, 9, 417, 10.1146/annurev.nu.09.070189.002221 Nielsen, 2004, Splanchnic lipolysis in human obesity, J Clin Invest, 113, 1582, 10.1172/JCI21047 Frayn, 1993, Periprandial regulation of lipid metabolism in insulin-treated diabetes mellitus, Metabolism, 42, 504, 10.1016/0026-0495(93)90110-A Bickerton, 2008, Adipose tissue fatty acid metabolism in insulin-resistant men, Diabetologia, 51, 1466, 10.1007/s00125-008-1040-x Lönnqvist, 1992, Lipolytic catecholamine resistance due to decreased β2-adrenoceptor expression in fat cells, J Clin Invest, 90, 2175, 10.1172/JCI116103 Langin, 2000, Millenium fat-cell lipolysis reveals unsuspected novel tracks, Horm Metab Res, 32, 443, 10.1055/s-2007-978670 Arner, 2005, Human fat cell lipolysis: biochemistry, regulation and clinical role, Best Pract Res Clin Endocrinol Metab, 19, 471, 10.1016/j.beem.2005.07.004 Tchernof, 2006, Regional differences in adipose tissue metabolism in women: minor effect of obesity and body fat distribution, Diabetes, 55, 1353, 10.2337/db05-1439 Boivin, 2007, Regional differences in adipose tissue metabolism in obese men, Metabolism, 56, 533, 10.1016/j.metabol.2006.11.015 Hellstrom, 1997, Lipolytic catecholamine resistance linked to alpha 2-adrenoceptor sensitivity—a metabolic predictor of weight loss in obese subjects, Int J Obes Relat Metab Disord, 21, 314, 10.1038/sj.ijo.0800407 Mauriège, 1999, Regional and gender variations in adipose tissue lipolysis in response to weight loss, J Lipid Res, 40, 1559, 10.1016/S0022-2275(20)33402-7 Zierath, 1998, Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway, Diabetologia, 41, 1343, 10.1007/s001250051075 Laviola, 2006, Insulin signaling in human visceral and subcutaneous adipose tissue in vivo, Diabetes, 55, 952, 10.2337/diabetes.55.04.06.db05-1414 Meek, 1999, Insulin regulation of regional free fatty acid metabolism, Diabetes, 48, 10, 10.2337/diabetes.48.1.10 Berndt, 2008, Adipose triglyceride lipase gene expression in human visceral obesity, Exp Clin Endocrinol Diabetes, 116, 203, 10.1055/s-2007-993148 Reynisdottir, 1997, Comparison of hormone-sensitive lipase activity in visceral and subcutaneous human adipose tissue, J Clin Endocrinol Metab, 82, 4162, 10.1210/jc.82.12.4162 Stich, 1997, Adipose tissue lipolysis and hormone-sensitive lipase expression during very-low-calorie diet in obese female identical twins, J Clin Endocrinol Metab, 82, 739, 10.1210/jc.82.3.739 Reynisdottir, 1995, Effects of weight reduction on the regulation of lipolysis in adipocytes of women with upper-body obesity, Clin Sci, 89, 421, 10.1042/cs0890421 Klein, 1996, Effect of weight loss on whole body and cellular lipid metabolism in severely obese humans, Am J Physiol, 270, E739 Horowitz, 2000, Lipid metabolism during endurance exercise, Am J Clin Nutr, 72, 558S, 10.1093/ajcn/72.2.558S Blaak, 2001, Gender differences in fat metabolism, Curr Opin Clin Nutr Metab Care, 4, 499, 10.1097/00075197-200111000-00006 Moro, 2007, Sex differences in lipolysis-regulating mechanisms in overweight subjects: effect of exercise intensity, Obesity (Silver Spring), 15, 2245, 10.1038/oby.2007.267 Henderson, 2007, Lipolysis and fatty acid metabolism in men and women during the postexercise recovery period, J Physiol, 584, 963, 10.1113/jphysiol.2007.137331 Stallknecht, 1995, Effect of training on epinephrine-stimulated lipolysis determined by microdialysis in human adipose tissue, Am J Physiol, 269, E1059 De Glisezinski, 1998, Endurance training changes in lipolytic responsiveness of obese adipose tissue, Am J Physiol, 275, E951 Stich, 1999, Endurance training increases the β-adrenergic lipolytic response in subcutaneous adipose tissue in obese subjects, Int J Obes, 23, 374, 10.1038/sj.ijo.0800829 Mauriège, 1997, Regional differences in adipose tissue metabolism between sedentary and endurance-trained women, Am J Physiol, 273, E497 De Glisezinski, 2001, Lack of alpha2-adrenergic antilipolytic effect during exercise in subcutaneous adipose tissue of trained men, J Appl Physiol, 91, 1760, 10.1152/jappl.2001.91.4.1760 Stich, 2000, Activation of alpha2-adrenergic receptors impairs exercise-induced lipolysis in SCAT of obese subjects, Am J Physiol, 279, R499 Moro, 2005, Training enhances ANP lipid-mobilizing action in adipose tissue of overweight men, Med Sci Sports Exerc, 37, 1126, 10.1249/01.mss.0000170124.51659.52 Moro, 2004, Atrial natriuretic peptide contributes to physiological control of lipid mobilization in humans, FASEB J, 18, 908, 10.1096/fj.03-1086fje De Glisezinski I, Larrouy D, Bajzova M, Koppo K, Polak J, Berlan M, et al. Epinephrine but not Norepinephrine is a determinant of exercise-induced lipid mobilization in human subcutaneous adipose tissue. J Physiol 2009. [Epub ahead of print]. Blaak, 2000, Adrenergically stimulated fat utilization and ageing, Ann Med, 32, 380, 10.3109/07853890008995942 Imbeault, 2000, Adipose tissue metabolism in young and middle-aged men after control for total body fatness, J Clin Endocrinol Metab, 85, 2455, 10.1210/jc.85.7.2455 Wolfe, 1997, Substrate utilization/insulin resistance in sepsis/trauma, Bailleres Clin Endocrinol Metab, 11, 645, 10.1016/S0950-351X(97)80926-3 Hagstrom-Toft, 1993, Adrenergic regulation of human adipose tissue metabolism in situ during mental stress, J Clin Endocrinol Metab, 76, 392, 10.1210/jc.76.2.392 Seematter, 2002, Metabolic effects of mental stress during over- and underfeeding in healthy women, Obes Res, 10, 49, 10.1038/oby.2002.7 Townsend, 1994, Changes in lipolytic sensitivity following repeated epinephrine infusion in humans, Am J Physiol, 266, E155 Stallnecht, 1997, Desensitization of human adipose tissue to adrenaline stimulation studied by microdialysis, J Physiol, 500, 271, 10.1113/jphysiol.1997.sp022017 Marion-Latard, 2001, A single bout of exercise induces beta-adrenergic desensitization in human adipose tissue, Am J Physiol Regul Integr Comp Physiol, 280, R166, 10.1152/ajpregu.2001.280.1.R166 Leibel, 1985, Alterations in adipocyte free fatty acid re-esterification associated with obesity and weight reduction in man, Am J Clin Nutr, 82, 198, 10.1093/ajcn/42.2.198 Ardilouze, 2004, Nitric oxide and beta-adrenergic stimulation are major regulators of preprandial and postprandial subcutaneous adipose tissue blood flow in humans, Circulation, 109, 47, 10.1161/01.CIR.0000105681.70455.73 Summers, 1999, Impaired postprandial tissue regulation of blood flow in insulin resistance. a determinant of cardiovascular risk?, Atherosclerosis, 147, 11, 10.1016/S0021-9150(99)00172-0 Jansson, 1992, Glycerol production in subcutaneous adipose tissue of lean and obese humans, J Clin Invest, 89, 1610, 10.1172/JCI115756 Large, 1999, Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects, J Lipid Res, 40, 2059, 10.1016/S0022-2275(20)32429-9 Watt, 2005, Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion, Diabetologia, 48, 105, 10.1007/s00125-004-1598-x Hellström, 1996, Adipocyte lipolysis in normal weight subjects with obesity among first degree relatives, Diabetologia, 39, 921, 10.1007/BF00403911 Steinberg, 2007, Adipocyte triglyceride lipase expression in human obesity, Am J Physiol Endocrinol Metab, 293, E958, 10.1152/ajpendo.00235.2007 Ek, 1997, Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance?, J Clin Endocrinol Metab, 82, 1147, 10.1210/jc.82.4.1147 Ek, 2002, A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance, Diabetes, 51, 484, 10.2337/diabetes.51.2.484 Arner, 2005, Effects of testosterone on fat cell lipolysis. Species differences and possible role in polycystic ovarian syndrome, Biochimie, 87, 39, 10.1016/j.biochi.2004.11.012 Bougnères, 1997, In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity, J Clin Invest, 99, 2568, 10.1172/JCI119444 Enoksson, 2000, Impaired in vivo stimulation of lipolysis in adipose tissue by selective β2-adrenergic agonist in obese adolescent girls, Diabetes, 49, 2149, 10.2337/diabetes.49.12.2149 Reynisdottir, 1994, Catecholamine resistance in fat cells of women with upper-body obesity due to decreased expression of beta2-adrenoceptors, Diabetologia, 37, 428, 10.1007/BF00408482 McKnight, 1998, Cyclic AMP, PKA, and the physiological regulation of adiposity, Recent Prog Horm Res, 53, 139 Mantovani, 2009, Protein kinase A regulatory subunits in human adipose tissue: decreased R2B expression and activity in adipocytes from obese subjects, Diabetes, 58, 620, 10.2337/db08-0585 Mauriège, 1991, Regional variation in adipose tissue lipolysis in lean and obese men, J Lipid Res, 32, 1625, 10.1016/S0022-2275(20)41648-7 Lönnqvist, 1997, Sex differences in visceral fat lipolysis and metabolic complications of obesity, Arterioscler Thromb Vasc Biol, 17, 1472, 10.1161/01.ATV.17.7.1472 Carel, 1999, Resistance to the lipolytic action of epinephrine: a new feature of protein Gs deficiency, J Clin Endocr Metab, 84, 4127, 10.1210/jc.84.11.4127 Horowitz, 2000, Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women, Am J Physiol, 278, E1144 Kaartinen, 1995, Beta-adrenergic responsiveness of adenylate cyclase in human adipocyte plasma membranes in obesity and after massive weight reduction, Metabolism, 44, 1288, 10.1016/0026-0495(95)90031-4 Dodt, 1999, Intraneural stimulation elicits an increase in subcutaneous interstitial glycerol levels in humans, J Physiol, 521, 545, 10.1111/j.1469-7793.1999.00545.x Schiffelers, 2003, Lipolytic and nutritive blood flow response to beta-adrenoceptor stimulation in situ in subcutaneous abdominal adipose tissue in obese men, Int J Obes Relat Metab Disord, 27, 227, 10.1038/sj.ijo.802230 Jocken, 2008, Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men, Diabetologia, 51, 320, 10.1007/s00125-007-0866-y Schiffelers, 2001, The effects of an increased NEFA concentration on thermogenesis and substrate oxidation in obese and lean men, Int J Obes, 25, 33, 10.1038/sj.ijo.0801528 Mauriège, 1992, Adipose tissue lipolysis after long-term overfeeding in identical twins, Int J Obes, 16, 219 Hellström, 2000, Influence of heredity for obesity on adipocyte lipolysis in lean and obese subjects, Int J Obes, 24, 340, 10.1038/sj.ijo.0801134 Arner, 2001, Genetic variance and lipolysis regulation: implications for obesity, Ann Med, 33, 542, 10.3109/07853890108995964 Jocken, 2007, Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation, Int J Obes (Lond), 31, 813, 10.1038/sj.ijo.0803499 Lima, 2007, Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations, Metabolism, 56, 757, 10.1016/j.metabol.2007.01.007 Dahlman, 2007, Obesity and polymorphisms in genes regulating human adipose tissue, Int J Obes (Lond), 31, 1629, 10.1038/sj.ijo.0803657 Stich, 2002, Hypocaloric diet reduces exercise-induced alpha 2-adrenergic antilipolytic effect and alpha 2-adrenergic receptor mRNA levels in adipose tissue of obese women, J Clin Endocrinol Metab, 87, 1274, 10.1210/jc.87.3.1274 Koutsari, 2008, Plasma NEFA storage in adipose tissue in the postprandial state: sex-related and regional differences, Diabetologia, 51, 2041, 10.1007/s00125-008-1126-5 Koutsari, 2008, Plasma free fatty acid storage in subcutaneous and visceral adipose tissue in postabsorptive women, Diabetes, 57, 1186, 10.2337/db07-0664 Smith, 2002, Impaired (‘diabetic’) insulin signaling and action occur in fat cells long before glucose intolerance—is insulin resistance initiated in the adipose tissue?, Int J Obes Relat Metab Disord, 26, 897, 10.1038/sj.ijo.0802028 Reynisdottir, 1994, Multiple lipolysis defects in the insulin resistance (metabolic) syndrome, J Clin Invest, 93, 2590, 10.1172/JCI117271 Langin, 2006, Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome, Pharmacol Res, 53, 482, 10.1016/j.phrs.2006.03.009 Karpe, 2004, The nicotinic acid receptor—a new mechanism for an old drug, Lancet, 363, 1892, 10.1016/S0140-6736(04)16359-9