Of mice and men: The physiological role of adipose triglyceride lipase (ATGL)

Zimmermann, 2004, Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase, Science, 306, 1383, 10.1126/science.1100747 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 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 Eichmann, 2012, Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases, J. Biol. Chem., 287, 41446, 10.1074/jbc.M112.400416 Taschler, 2015, Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells, Biochim. Biophys. Acta - Mol. Cell Biol. Lipids, 1851, 937, 10.1016/j.bbalip.2015.02.017 Notari, 2006, Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor, J. Biol. Chem., 281, 38022, 10.1074/jbc.M600353200 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 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 Martinez-Lopez, 2016, Autophagy in the CNS and periphery coordinate lipophagy and lipolysis in the brown adipose tissue and liver, Cell Metab., 23, 113, 10.1016/j.cmet.2015.10.008 Soni, 2009, Coatomer-dependent protein delivery to lipid droplets, J. Cell Sci., 122, 1834, 10.1242/jcs.045849 Ellong, 2011, Interaction between the triglyceride lipase ATGL and the arf1 activator GBF1, PLoS One, 6, 10.1371/journal.pone.0021889 Beller, 2008, COPI complex is a regulator of lipid homeostasis, PLoS Biol., 6, 10.1371/journal.pbio.0060292 Xie, 2014, Identification of a novel phosphorylation site in adipose triglyceride lipase as a regulator of lipid droplet localization, AJP Endocrinol. Metab., 306, E1449, 10.1152/ajpendo.00663.2013 Al-Zoughbi, 2016, Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia, Oncotarget, 7, 33832, 10.18632/oncotarget.9418 Schlager, 2015, Adipose triglyceride lipase acts on neutrophil lipid droplets to regulate substrate availability for lipid mediator synthesis, J. Leukoc. Biol., 98, 837, 10.1189/jlb.3A0515-206R Dichlberger, 2014, Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells, J. Lipid Res., 55, 2471, 10.1194/jlr.M048553 Lammers, 2011, Macrophage adipose triglyceride lipase deficiency attenuates atherosclerotic lesion development in low-density lipoprotein receptor knockout mice, Arterioscler. Thromb. Vasc. Biol., 31, 67, 10.1161/ATVBAHA.110.215814 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 Obrowsky, 2013, Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARalpha signaling, J. Lipid Res., 54, 425, 10.1194/jlr.M031716 Roy, 2017, Coordinated transcriptional control of adipocyte triglyceride lipase (Atgl) by transcription factors Sp1 and peroxisome proliferator-activated receptor ? (PPAR?) during adipocyte differentiation, J. Biol. Chem., 292, 14827, 10.1074/jbc.M117.783043 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. Metab., 291, E115 Singh, 2014, Fat-specific protein 27 inhibits lipolysis by facilitating the inhibitory effect of transcription factor egr1 on transcription of adipose triglyceride lipase, J. Biol. Chem., 289, 14481, 10.1074/jbc.C114.563080 Chakrabarti, 2013, Insulin inhibits lipolysis in adipocytes via the evolutionarily conserved mTORC1-Egr1-ATGL-mediated pathway, Mol. Cell. Biol., 33, 3659, 10.1128/MCB.01584-12 Eguchi, 2011, Transcriptional control of adipose lipid handling by IRF4, Cell Metab., 13, 249, 10.1016/j.cmet.2011.02.005 Chakrabarti, 2011, SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL, J. Lipid Res., 52, 1693, 10.1194/jlr.M014647 van der Heide, 2004, The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation, Biochem. J., 380, 297, 10.1042/bj20040167 Chakrabarti, 2009, FoxO1 controls insulin-dependent adipose triglyceride lipase (ATGL) expression and lipolysis in adipocytes, J. Biol. Chem., 284, 13296, 10.1074/jbc.C800241200 Chen, 2016, LncRNA SRA promotes hepatic steatosis through repressing the expression of adipose triglyceride lipase (ATGL), Sci. Rep., 6, 1 Kaltenecker, 2017, Adipocyte STAT5 deficiency promotes adiposity and impairs lipid mobilisation in mice, Diabetologia, 60, 296, 10.1007/s00125-016-4152-8 Nielsen, 2011, Fasting, but not exercise, increases adipose triglyceride lipase (ATGL) protein and reduces G(0)/G(1) switch gene 2 (G0S2) protein and mRNA content in human adipose tissue, J. Clin. Endocrinol. Metab., 96, E1293, 10.1210/jc.2011-0149 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 Bartz, 2007, Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic, J. Lipid Res., 48, 837, 10.1194/jlr.M600413-JLR200 Pagnon, 2012, Identification and functional characterization of protein kinase a phosphorylation sites in the major lipolytic protein, adipose triglyceride lipase, Endocrinology, 153, 4278, 10.1210/en.2012-1127 Kim, 2016, AMPK phosphorylates desnutrin/ATGL and hormone-sensitive lipase to regulate lipolysis and fatty acid oxidation within adipose tissue, Mol. Cell. Biol., 36, 1961, 10.1128/MCB.00244-16 Ahmadian, 2011, Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype, Cell Metab., 13, 739, 10.1016/j.cmet.2011.05.002 Nagy, 2014, Adipose triglyceride lipase activity is inhibited by long-chain acyl-coenzyme A, Biochim. Biophys. Acta, 1841, 588, 10.1016/j.bbalip.2014.01.005 Dai, 2013, Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: A novel mechanistic insight into progressive obesity, Mol. Cell. Endocrinol., 377, 123, 10.1016/j.mce.2013.07.001 Ghosh, 2016, Ubiquitin ligase COP1 controls hepatic fat metabolism by targeting ATGL for degradation, Diabetes, 65, 3561, 10.2337/db16-0506 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 Hofer, 2015, Fatty acid-binding proteins interact with comparative gene identification-58 linking lipolysis with lipid ligand shuttling, J. Biol. Chem., 290, 18438, 10.1074/jbc.M114.628958 Olzmann, 2013, Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover, Proc. Natl. Acad. Sci., 110, 1345, 10.1073/pnas.1213738110 Granneman, 2008, Location, location: protein trafficking and lipolysis in adipocytes, Trends Endocrinol. Metab., 19, 3, 10.1016/j.tem.2007.10.006 Pollak, 2015, The interplay of protein kinase A and perilipin 5 regulates cardiac lipolysis, J. Biol. Chem., 290, 1295, 10.1074/jbc.M114.604744 Sanders, 2015, Endogenous and synthetic ABHD5 ligands regulate ABHD5-perilipin interactions and lipolysis in fat and muscle, Cell Metab., 22, 851, 10.1016/j.cmet.2015.08.023 Granneman, 2011, Interactions of perilipin-5 (Plin5) with adipose triglyceride lipase, J. Biol. Chem., 286, 5126, 10.1074/jbc.M110.180711 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 Zhang, 2017, Inhibition of intracellular lipolysis promotes human cancer cell adaptation to hypoxia, elife, 6, 10.7554/eLife.31132 Padmanabha Das, 2018, Hypoxia-inducible lipid droplet-associated protein inhibits adipose triglyceride lipase, J. Lipid Res., 59, 531, 10.1194/jlr.M082388 Subramanian, 2013, Pigment epithelium-derived factor (PEDF) prevents retinal cell death via PEDF receptor (PEDF-R): identification of a functional ligand binding site, J. Biol. Chem., 288, 23928, 10.1074/jbc.M113.487884 Borg, 2011, Pigment epithelium-derived factor regulates lipid metabolism via adipose triglyceride lipase, Diabetes, 60, 1458, 10.2337/db10-0845 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 Schweiger, 2012, G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase, J. Lipid Res., 53, 2307, 10.1194/jlr.M027409 Grahn, 2014, Fat-specific protein 27 (FSP27) interacts with adipose triglyceride lipase (ATGL) to regulate lipolysis and insulin sensitivity in human adipocytes, J. Biol. Chem., 289, 12029, 10.1074/jbc.M113.539890 Mayer, 2013, Development of small-molecule inhibitors targeting adipose triglyceride lipase, Nat. Chem. Biol., 9, 785, 10.1038/nchembio.1359 Kaneko, 2014, A novel mutation in PNPLA2 causes neutral lipid storage disease with myopathy and triglyceride deposit cardiomyovasculopathy: a case report and literature review, Neuromuscul. Disord., 24, 634, 10.1016/j.nmd.2014.04.001 Missaglia, 2015, Novel missense mutations in PNPLA2 causing late onset and clinical heterogeneity of neutral lipid storage disease with myopathy in three siblings, Mol. Genet. Metab., 115, 110, 10.1016/j.ymgme.2015.05.001 Xu, 2015, Muscle MRI in neutral lipid storage disease with myopathy carrying mutation c.187+1G>A, Muscle Nerve, 51, 922, 10.1002/mus.24507 Tan, 2018, Patients with neutral lipid storage disease with myopathy (NLSDM) in Southwestern China, Clin. Neurol. Neurosurg., 168, 102, 10.1016/j.clineuro.2018.03.001 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, 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 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 Haemmerle, 2006, Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase, Science, 312, 734, 10.1126/science.1123965 Wu, 2012, Fasting energy homeostasis in mice with adipose deficiency of desnutrin/adipose triglyceride lipase, Endocrinology, 153, 2198, 10.1210/en.2011-1518 Schoiswohl, 2015, Impact of reduced ATGL-mediated adipocyte lipolysis on obesity-associated insulin resistance and inflammation in male mice, Endocrinology, 156, 3610, 10.1210/en.2015-1322 Schreiber, 2017, Cold-induced thermogenesis depends on ATGL-mediated lipolysis in cardiac muscle, but not brown adipose tissue, Cell Metab., 26, 753, 10.1016/j.cmet.2017.09.004 Ryden, 2007, Comparative studies of the role of hormone-sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis, Am. J. Physiol. Metab., 292, E1847 Coassin, 2010, Investigation and functional characterization of rare genetic variants in the adipose triglyceride lipase in a large healthy working population, PLoS Genet., 6, 1, 10.1371/journal.pgen.1001239 Natali, 2013, Metabolic consequences of adipose triglyceride lipase deficiency in humans: an in vivo study in patients with neutral lipid storage disease with myopathy, J. Clin. Endocrinol. Metab., 98, E1540, 10.1210/jc.2013-1444 Georgiadi, 2012, Mechanisms of gene regulation by fatty acids, Adv. Nutr., 3, 127, 10.3945/an.111.001602 Fan, 2015, PPARs and ERRs: molecular mediators of mitochondrial metabolism, Curr. Opin. Cell Biol., 33, 49, 10.1016/j.ceb.2014.11.002 Haemmerle, 2011, ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1, Nat. Med., 17, 1076, 10.1038/nm.2439 Mottillo, 2012, Lipolytic products activate peroxisome proliferator-activated receptor (PPAR) α and δ in brown adipocytes to match fatty acid oxidation with supply, J. Biol. Chem., 287, 25038, 10.1074/jbc.M112.374041 Ong, 2011, Adipose triglyceride lipase is a major hepatic lipase that regulates triacylglycerol turnover and fatty acid signaling and partitioning, Hepatology, 53, 116, 10.1002/hep.24006 Chandak, 2010, Efficient phagocytosis requires triacylglycerol hydrolysis by adipose triglyceride lipase, J. Biol. Chem., 285, 20192, 10.1074/jbc.M110.107854 Aflaki, 2011, Triacylglycerol accumulation activates the mitochondrial apoptosis pathway in macrophages, J. Biol. Chem., 286, 7418, 10.1074/jbc.M110.175703 Tang, 2013, Desnutrin/ATGL activates PPARδ to promote mitochondrial function for insulin secretion in islet β cells, Cell Metab., 18, 883, 10.1016/j.cmet.2013.10.012 Schreiber, 2015, Hypophagia and metabolic adaptations in mice with defective ATGL-mediated lipolysis cause resistance to HFD-induced obesity, Proc. Natl. Acad. Sci. U. S. A., 112, 13850, 10.1073/pnas.1516004112 Schweiger, 2017, Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice, Nat. Commun., 8 Hirano, 2014, Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-γ in patients with triglyceride deposit cardiomyovasculopathy, Biochem. Biophys. Res. Commun., 443, 574, 10.1016/j.bbrc.2013.12.003 Alberti, 2009, Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International, Circulation, 120, 1640, 10.1161/CIRCULATIONAHA.109.192644 Ahmadian, 2009, Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity, Diabetes, 58, 855, 10.2337/db08-1644 Harada, 2003, Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice, Am. J. Physiol. Metab., 285, E1182 Osuga, 2000, Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity, Proc. Natl. Acad. Sci. U. S. A., 97, 787, 10.1073/pnas.97.2.787 Zimmermann, 2003, Decreased fatty acid esterification compensates for the reduced lipolytic activity in hormone-sensitive lipase-deficient white adipose tissue, J. Lipid Res., 44, 2089, 10.1194/jlr.M300190-JLR200 Albert, 2014, Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes, N. Engl. J. Med., 370, 2307, 10.1056/NEJMoa1315496 Mottillo, 2014, Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic ß3-adrenergic receptor activation, J. Lipid Res., 55, 2276, 10.1194/jlr.M050005 Shen, 2011, Hormone-sensitive lipase modulates adipose metabolism through PPARγ, Biochim. Biophys. Acta, 1811, 9, 10.1016/j.bbalip.2010.10.001 Kienesberger, 2009, Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling, J. Biol. Chem., 284, 30218, 10.1074/jbc.M109.047787 Etschmaier, 2011, Adipose triglyceride lipase affects triacylglycerol metabolism at brain barriers, J. Neurochem., 119, 1016, 10.1111/j.1471-4159.2011.07498.x Ryan, 2011, A role for central nervous system PPAR-γ in the regulation of energy balance, Nat. Med., 17, 623, 10.1038/nm.2349 Myers, 2012, Central nervous system control of metabolism, Nature, 491, 357, 10.1038/nature11705 Xie, 2014, Intestinal Cgi-58 deficiency reduces postprandial lipid absorption, PLoS One, 9 Cooke, 2016, Fatty acids and chronic low grade inflammation associated with obesity and the metabolic syndrome, Eur. J. Pharmacol., 785, 207, 10.1016/j.ejphar.2016.04.021 Osborn, 2012, The cellular and signaling networks linking the immune system and metabolism in disease, Nat. Med., 18, 363, 10.1038/nm.2627 Perry, 2015, Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes, Cell, 160, 745, 10.1016/j.cell.2015.01.012 Kosteli, 2010, Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue, J. Clin. Invest., 120, 3466, 10.1172/JCI42845 Cinti, 2005, Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans, J. Lipid Res., 46, 2347, 10.1194/jlr.M500294-JLR200 Kotzbeck, 2018, Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation, J. Lipid Res., 59, 784, 10.1194/jlr.M079665 Aflaki, 2011, Impaired Rho GTPase activation abrogates cell polarization and migration in macrophages with defective lipolysis, Cell. Mol. Life Sci., 68, 3933, 10.1007/s00018-011-0688-4 Zimmet, 2016, Diabetes mellitus statistics on prevalence and mortality: facts and fallacies, Nat. Rev. Endocrinol., 12, 616, 10.1038/nrendo.2016.105 Randle, 1963, The Glucose Fatty-Acid Cycle Its Role in Insulin Sensitivity and the Metabolic Disturbances of Diabetes Mellitus, Lancet, 281, 785, 10.1016/S0140-6736(63)91500-9 Unger, 1995, Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications, Diabetes, 44, 863, 10.2337/diab.44.8.863 Chaurasia, 2015, Ceramides – lipotoxic inducers of metabolic disorders, Trends Endocrinol. Metab., 26, 538, 10.1016/j.tem.2015.07.006 Muoio, 2010, Intramuscular triacylglycerol and insulin resistance: guilty as charged or wrongly accused?, Biochim. Biophys. Acta, 1801, 281, 10.1016/j.bbalip.2009.11.007 Perry, 2014, The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes, Nature, 510, 84, 10.1038/nature13478 Prentki, 2013, Metabolic signaling in fuel-induced insulin secretion, Cell Metab., 18, 162, 10.1016/j.cmet.2013.05.018 Hoy, 2011, Adipose triglyceride lipase-null mice are resistant to high-fat diet-induced insulin resistance despite reduced energy expenditure and ectopic lipid accumulation, Endocrinology, 152, 48, 10.1210/en.2010-0661 Dobbins, 1998, Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans, Diabetes, 47, 1613, 10.2337/diabetes.47.10.1613 Stein, 1996, Essentially of circulating fatty acids for glucose-stimulated insulin secretion in fasted rats, J. Clin. Invest., 97, 2728, 10.1172/JCI118727 Itoh, 2003, Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40, Nature, 422, 173, 10.1038/nature01478 Ichimura, 2012, Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human, Nature, 483, 350, 10.1038/nature10798 Noushmehr, 2005, Fatty acid translocase (FAT/CD36) is localized on insulin-containing granules in human pancreatic beta-cells and mediates fatty acid effects on insulin secretion, Diabetes, 54, 472, 10.2337/diabetes.54.2.472 Heine, 2018, Lipolysis triggers a systemic insulin response essential for efficient energy replenishment of activated brown adipose tissue in mice, Cell Metab., 28, 644, 10.1016/j.cmet.2018.06.020 Attané, 2016, A beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion in mice, Diabetologia, 59, 2654, 10.1007/s00125-016-4105-2 Turpin, 2011, Adipose triacylglycerol lipase is a major regulator of hepatic lipid metabolism but not insulin sensitivity in mice, Diabetologia, 54, 146, 10.1007/s00125-010-1895-5 Ong, 2013, Hepatic ATGL knockdown uncouples glucose intolerance from liver TAG accumulation, FASEB J., 27, 313, 10.1096/fj.12-213454 Wu, 2011, Deficiency of liver adipose triglyceride lipase in mice causes progressive hepatic steatosis, Hepatology, 54, 122, 10.1002/hep.24338 Sitnick, 2013, Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity, Diabetes, 62, 3350, 10.2337/db13-0500 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 van de Weijer, 2013, Effects of bezafibrate treatment in a patient and a carrier with mutations in the PNPLA2 gene, causing neutral lipid storage disease with myopathy, Circ. Res., 112, e51, 10.1161/CIRCRESAHA.113.300944 Cohen, 2011, Human fatty liver disease: old questions and new insights, Science, 332, 1519, 10.1126/science.1204265 Haemmerle, 2018, Genetically modified mouse models to study hepatic neutral lipid mobilization, Biochim. Biophys. Acta Mol. basis Dis., 10.1016/j.bbadis.2018.06.001 Eichmann, 2015, ATGL and CGI-58 are lipid droplet proteins of the hepatic stellate cell line HSC-T6, J. Lipid Res., 56, 1972, 10.1194/jlr.M062372 Mello, 2008, Expression of carboxylesterase and lipase genes in rat liver cell-types, Biochem. Biophys. Res. Commun., 374, 460, 10.1016/j.bbrc.2008.07.024 Heier, 2015, G0/G1 switch gene-2 regulates cardiac lipolysis, J. Biol. Chem., 10.1074/jbc.M115.671842 Janssen, 2013, Symptomatic lipid storage in carriers for the PNPLA2 gene, Eur. J. Hum. Genet., 21, 807, 10.1038/ejhg.2012.256 Fiorillo, 2013, Subclinical myopathy in a child with neutral lipid storage disease and mutations in the PNPLA2 gene, Biochem. Biophys. Res. Commun., 430, 241, 10.1016/j.bbrc.2012.10.127 Reilich, 2011, The phenotypic spectrum of neutral lipid storage myopathy due to mutations in the PNPLA2 gene, J. Neurol., 258, 1987, 10.1007/s00415-011-6055-4 Donnelly, 2005, Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease, J. Clin. Invest., 115, 1343, 10.1172/JCI23621 Jaeger, 2015, Fasting-induced G0/G1 switch gene 2 and FGF21 expression in the liver are under regulation of adipose tissue derived fatty acids, J. Hepatol., 63, 437, 10.1016/j.jhep.2015.02.035 Reid, 2008, Hepatic overexpression of hormone-sensitive lipase and adipose triglyceride lipase promotes fatty acid oxidation, stimulates direct release of free fatty acids, and ameliorates steatosis, J. Biol. Chem., 283, 13087, 10.1074/jbc.M800533200 Khan, 2015, ATGL-catalyzed lipolysis regulates SIRT1 to control PGC-1α/PPAR-α signaling, Diabetes, 64, 418, 10.2337/db14-0325 Singh, 2009, Autophagy regulates lipid metabolism, Nature, 458, 1131, 10.1038/nature07976 Lee, 2015, 516 Lee, 2008, A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy, Proc. Natl. Acad. Sci. U. S. A., 105, 3374, 10.1073/pnas.0712145105 Zechner, 2017, Cytosolic lipolysis and lipophagy: Two sides of the same coin, Nat. Rev. Mol. Cell Biol., 18, 671, 10.1038/nrm.2017.76 Kaushik, 2015, Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis, Nat. Cell Biol., 17, 759, 10.1038/ncb3166 Sathyanarayan, 2017, ATGL promotes autophagy/lipophagy via SIRT1 to control hepatic lipid droplet catabolism, Cell Rep., 19, 1, 10.1016/j.celrep.2017.03.026 Martinez-Lopez, 2015, Autophagy and lipid droplets in the liver, Annu. Rev. Nutr., 35, 215, 10.1146/annurev-nutr-071813-105336 Guo, 2013, Deficiency of liver comparative gene identification-58 causes steatohepatitis and fibrosis in mice, J. Lipid Res., 54, 2109, 10.1194/jlr.M035519 Jha, 2014, Role of adipose tissue in methionine-choline-deficient model of non-alcoholic steatohepatitis (NASH), Biochim. Biophys. Acta, 1842, 959, 10.1016/j.bbadis.2014.02.012 Fuchs, 2012, Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in mice, Hepatology, 56, 270, 10.1002/hep.25601 Puche, 2013, Hepatic stellate cells and liver fibrosis Tuohetahuntila, 2016, ATGL and DGAT1 are involved in the turnover of newly synthesized triacylglycerols in hepatic stellate cells, J. Lipid Res., 57, 1162, 10.1194/jlr.M066415 Pirazzi, 2014, PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells, Hum. Mol. Genet., 23, 4077, 10.1093/hmg/ddu121 Kovarova, 2015, The genetic variant I148M in PNPLA3 is associated with increased hepatic retinyl-palmitate storage in humans, J. Clin. Endocrinol. Metab., 100, E1568, 10.1210/jc.2015-2978 Kato, 2008, Reduced hepatic expression of adipose tissue triglyceride lipase and CGI-58 may contribute to the development of non-alcoholic fatty liver disease in patients with insulin resistance, Scand. J. Gastroenterol., 43, 1018, 10.1080/00365520802008140 Schulze, 2016, Lipid use and misuse by the heart, Circ. Res., 118, 1736, 10.1161/CIRCRESAHA.116.306842 Kienesberger, 2013, Early structural and metabolic cardiac remodelling in response to inducible adipose triglyceride lipase ablation, Cardiovasc. Res., 99, 442, 10.1093/cvr/cvt124 Pennisi, 2015, A myopathy with unusual features caused by PNPLA2 gene mutations, Muscle Nerve, 51, 609, 10.1002/mus.24477 Zierler, 2013, Functional cardiac lipolysis in mice critically depends on comparative gene identification-58, J. Biol. Chem., 288, 9892, 10.1074/jbc.M112.420620 Schweiger, 2009, Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/ PNPLA2 or CGI-58 / ABHD5, Am. J. Physiol. Metab., 297, E289 Pollak, 2013, Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier, J. Lipid Res., 54, 1092, 10.1194/jlr.M034710 Wölkart, 2012, Cardiac dysfunction in adipose triglyceride lipase deficiency: treatment with a PPARα agonist, Br. J. Pharmacol., 165, 380, 10.1111/j.1476-5381.2011.01490.x Suzuki, 2018, Tricaprin rescues myocardial abnormality in a mouse model of triglyceride deposit cardiomyovasculopathy, J. Oleo Sci., 67, 983, 10.5650/jos.ess18037 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 Kienesberger, 2012, Myocardial ATGL overexpression decreases the reliance on fatty acid oxidation and protects against pressure overload-induced cardiac dysfunction, Mol. Cell. Biol., 32, 740, 10.1128/MCB.06470-11 Pulinilkunnil, 2013, Myocardial adipose triglyceride lipase overexpression protects diabetic mice from the development of lipotoxic cardiomyopathy, Diabetes, 62, 1464, 10.2337/db12-0927 Pulinilkunnil, 2014, Cardiac-specific adipose triglyceride lipase overexpression protects from cardiac steatosis and dilated cardiomyopathy following diet-induced obesity, Int. J. Obes., 38, 205, 10.1038/ijo.2013.103 Nagendran, 2013, Cardiomyocyte specific adipose triglyceride lipase overexpression prevents doxorubicin induced cardiac dysfunction in female mice, Heart, 99, 1041, 10.1136/heartjnl-2013-303843 Parajuli, 2018, Atglistatin ameliorates functional decline in heart failure via adipocyte-specific inhibition of adipose triglyceride lipase, Am. J. Physiol. Heart Circ. Physiol., 10.1152/ajpheart.00308.2018 Salatzki, 2018, Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure, PLoS Genet., 14, 10.1371/journal.pgen.1007171 Biswas, 2016, PPARa-ATGL pathway improves muscle mitochondrial metabolism: Implication in aging, FASEB J., 30, 3822, 10.1096/fj.201600571RR Huijsman, 2009, Adipose triacylglycerol lipase deletion alters whole body energy metabolism and impairs exercise performance in mice, Am. J. Physiol. Metab., 297, E505 Dubé, 2015, Adipose triglyceride lipase deletion from adipocytes, but not skeletal myocytes, impairs acute exercise performance in mice, Am. J. Physiol. - Endocrinol. Metab., 308, E879, 10.1152/ajpendo.00530.2014 Ohkuma, 2008, Distal lipid storage myopathy due to PNPLA2 mutation, Neuromuscul. Disord., 18, 671, 10.1016/j.nmd.2008.06.382 Campagna, 2008, Novel mutations in the adipose triglyceride lipase gene causing neutral lipid storage disease with myopathy, Biochem. Biophys. Res. Commun., 377, 843, 10.1016/j.bbrc.2008.10.081 Ohkuma, 2009, Clinical and genetic analysis of lipid storage myopathies, Muscle Nerve, 39, 333, 10.1002/mus.21167 Ash, 2012, A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy, Arch. Neurol., 69, 1190, 10.1001/archneurol.2011.2600 Pasanisi, 2016, Severe cardiomyopathy in a young patient with complete deficiency of adipose triglyceride lipase due to a novel mutation in PNPLA2 gene, Int. J. Cardiol., 207, 165, 10.1016/j.ijcard.2016.01.137 Laforet, 2012, Blocked muscle fat oxidation during exercise in neutral lipid storage disease, Arch. Neurol., 69, 530, 10.1001/archneurol.2011.631 Jocken, 2008, Adipose triglyceride lipase (ATGL) expression in human skeletal muscle is type I (oxidative) fiber specific, Histochem. Cell Biol., 129, 535, 10.1007/s00418-008-0386-y Aquilano, 2016, Adipose triglyceride lipase decrement affects skeletal muscle homeostasis during aging through FAs-PPARa-PGC-1a antioxidant response, Oncotarget, 7, 23019, 10.18632/oncotarget.8552 Barbera, 2001, Peroxisome proliferator-activated receptor alpha activates transcription of the brown fat uncoupling protein-1 gene. A link between regulation of the thermogenic and lipid oxidation pathways in the brown fat cell, J. Biol. Chem., 276, 1486, 10.1074/jbc.M006246200 Crichton, 2017, The molecular features of uncoupling protein 1 support a conventional mitochondrial carrier-like mechanism, Biochimie, 134, 35, 10.1016/j.biochi.2016.12.016 Wang, 2001, The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice, Obes. Res., 9, 119, 10.1038/oby.2001.15 Li, 2014, Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes, EMBO Rep., 15, 1069, 10.15252/embr.201438775 Shin, 2017, Lipolysis in brown adipocytes is not essential for cold-induced thermogenesis in mice, Cell Metab., 26, 764, 10.1016/j.cmet.2017.09.002 Simcox, 2017, Global analysis of plasma lipids identifies liver-derived acylcarnitines as a fuel source for brown fat thermogenesis, Cell Metab., 26, 509, 10.1016/j.cmet.2017.08.006 Cannon, 2017, What ignites UCP1?, Cell Metab., 26, 697, 10.1016/j.cmet.2017.10.012 Fedorenko, 2012, Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria, Cell, 151, 400, 10.1016/j.cell.2012.09.010 Belfrage, 1977, Hormone-sensitive lipase of rat adipose tissue: identification and some properties of the enzyme protein, FEBS Lett., 75, 259, 10.1016/0014-5793(77)80099-9 Wu, 2017, Epistatic interaction between the lipase-encoding genes Pnpla2 and lipe causes liposarcoma in mice, PLoS Genet., 13, 10.1371/journal.pgen.1006716 Cannon, 2011, Nonshivering thermogenesis and its adequate measurement in metabolic studies, J. Exp. Biol., 214, 242, 10.1242/jeb.050989 Vegliante, 2018, Hints on ATGL implications in cancer: beyond bioenergetic clues, Cell Death Dis., 9, 316, 10.1038/s41419-018-0345-z Barrallo-Gimeno, 2005, The snail genes as inducers of cell movement and survival: implications in development and cancer, Development, 132, 3151, 10.1242/dev.01907 Sun, 2016, Adipose snail regulates lipolysis and lipid partitioning by suppressing adipose triacylglycerol lipase expression, Cell Rep., 17, 2015, 10.1016/j.celrep.2016.10.070 Lettieri Barbato, 2014, Proline oxidase-adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation, Cell Death Differ., 21, 113, 10.1038/cdd.2013.137 Yadav, 2018, FoxO transcription factors in cancer metabolism, Semin. Cancer Biol., 50, 65, 10.1016/j.semcancer.2018.01.004 Chen, 2017, Loss of ABHD5 promotes the aggressiveness of prostate cancer cells, Sci. Rep., 7, 13021, 10.1038/s41598-017-13398-w Liu, 2018, Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation, Mol. Cancer, 17, 1, 10.1186/s12943-018-0838-5 Ou, 2014, Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition, Cell Rep., 9, 1798, 10.1016/j.celrep.2014.11.016 Zagani, 2015, Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells, Oncotarget, 6, 28282, 10.18632/oncotarget.5061 Wang, 2017, Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells, JCI Insight., 2, 10.1172/jci.insight.87489 Tomin, 2018, Deletion of adipose triglyceride lipase links triacylglycerol accumulation to a more-aggressive phenotype in A549 lung carcinoma cells, J. Proteome Res., 17, 1415, 10.1021/acs.jproteome.7b00782 Peng, 2016, ABHD5 interacts with BECN1 to regulate autophagy and tumorigenesis of colon cancer independent of PNPLA2, Autophagy, 12, 2167, 10.1080/15548627.2016.1217380 Yim, 2016, GOS2 suppresses oncogenic transformation by repressing a MYC-regulated transcriptional program, Cancer Res., 76, 1204, 10.1158/0008-5472.CAN-15-2265 Yim, 2017, G0S2 represses PI3K/mTOR signaling and increases sensitivity to PI3K/mTOR pathway inhibitors in breast cancer, Cell Cycle, 16, 2146, 10.1080/15384101.2017.1371884 Fearon, 2011, Definition and classification of cancer cachexia: an international consensus, Lancet Oncol., 12, 489, 10.1016/S1470-2045(10)70218-7 Petruzzelli, 2016, Mechanisms of metabolic dysfunction in cancer-associated cachexia, Genes Dev., 30, 489, 10.1101/gad.276733.115 Das, 2011, Adipose triglyceride lipase contributes to cancer-associated cachexia, Science, 333, 233, 10.1126/science.1198973 Kir, 2014, Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia, Nature, 513, 100, 10.1038/nature13528 Petruzzelli, 2014, A switch from white to brown fat increases energy expenditure in cancer-associated cachexia, Cell Metab., 20, 433, 10.1016/j.cmet.2014.06.011 Tsoli, 2014, Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation, PLoS One, 9, 10.1371/journal.pone.0092966 Fearon, 2012, 153 Arora, 2018, Cachexia-associated adipose loss induced by tumor-secreted leukemia inhibitory factor is counterbalanced by decreased leptin, J. Clin. Investig. Insight., 3 Baracos, 2018, Cancer-associated cachexia, Nat. Rev. Dis. Prim., 4, 17105, 10.1038/nrdp.2017.105 Masaki, 2017, Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male fertility: a study using adipose triglyceride lipase deficient mice, Mol. Hum. Reprod., 23, 452, 10.1093/molehr/gax031 Rozenszajn, 1966, Jordans' anomaly in white blood cells. Report of case, Blood, 28, 258, 10.1182/blood.V28.2.258.258 Chanarin, 1975, Neutral-lipid storage disease: A new disorder of lipid metabolism, Br. Med. J., 1, 553, 10.1136/bmj.1.5957.553 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 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 Grond, 2017, Skin barrier development depends on CGI-58 protein expression during late-stage keratinocyte differentiation, J. Invest. Dermatol., 137, 403, 10.1016/j.jid.2016.09.025 Kien, 2018, ABHD5 stimulates PNPLA1-mediated omega-O-acylceramide biosynthesis essential for a functional skin permeability barrier, J. Lipid Res., 10.1194/jlr.M089771 Hirabayashi, 2018, The role of PNPLA1 in ω-O-acylceramide synthesis and skin barrier function, Biochim. Biophys. Acta. Mol. Cell Biol. Lipids. Pham, 2017, Defining a mechanistic link between pigment epithelium–derived factor, docosahexaenoic acid, and corneal nerve regeneration, J. Biol. Chem., 292, 18486, 10.1074/jbc.M117.801472 Bilak, 1999, Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration, J. Neuropathol. Exp. Neurol., 58, 719, 10.1097/00005072-199907000-00006 Yabe, 2001, NFκB activation is required for the neuroprotective effects of pigment epithelium-derived factor (PEDF) on cerebellar granule neurons, J. Biol. Chem., 276, 43313, 10.1074/jbc.M107831200 DeCoster, 1999, Neuroprotection by pigment epithelial-derived factor against glutamate toxicity in developing primary hippocampal neurons, J. Neurosci. Res., 56, 604, 10.1002/(SICI)1097-4547(19990615)56:6<604::AID-JNR6>3.0.CO;2-B Laforêt, 2013, Neutral lipid storage disease with myopathy: a whole-body nuclear MRI and metabolic study, Mol. Genet. Metab., 108, 125, 10.1016/j.ymgme.2012.12.004 Hirano, 2008, Triglyceride deposit cardiomyovasculopathy, N. Engl. J. Med., 359, 2396, 10.1056/NEJMc0805305 Tavian, 2012, Contribution of novel ATGL missense mutations to the clinical phenotype of NLSD-M: a strikingly low amount of lipase activity may preserve cardiac function, Hum. Mol. Genet., 21, 5318, 10.1093/hmg/dds388 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 Chen, 2010, A novel PNPLA2 mutation causes neutral lipid storage disease with myopathy (NLSDM) presenting muscular dystrophic features with lipid storage and rimmed vacuoles, Clin. Neuropathol., 29, 351, 10.5414/NPP29351 Akman, 2010, Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene, Neuromuscul. Disord., 20, 397, 10.1016/j.nmd.2010.04.004 Lin, 2012, Novel PNPLA2 gene mutations in Chinese Han patients causing neutral lipid storage disease with myopathy, J. Hum. Genet., 57, 679, 10.1038/jhg.2012.84 Latimer, 2018, Neutral lipid storage disease with myopathy: further phenotypic characterization of a rare PNPLA2 variant, Neuromuscul. Disord., 28, 606, 10.1016/j.nmd.2018.04.010 Tavian, 2013, A late-onset case of neutral lipid storage disease with myopathy,dropped head syndrome, and peripheral nerve involvement, J. Genet. Syndr. Gene Ther., 04, 1 Massa, 2016, Neutral lipid-storage disease with myopathy and extended phenotype with novel PNPLA2 mutation, Muscle Nerve, 53, 644, 10.1002/mus.24983