ENTRY       hsa04923                    Pathway
NAME        Regulation of lipolysis in adipocytes - Homo sapiens (human)
DESCRIPTION Lipolysis in adipocytes, the hydrolysis of triacylglycerol (TAG) to release fatty acids (FAs) and glycerol for use by other organs as energy substrates, is a unique function of white adipose tissue. Lipolysis is under tight hormonal control. During fasting, catecholamines, by binding to Gs-coupled-adrenergic receptors (-AR), activate adenylate cyclase (AC) to increase cAMP and activate protein kinase A (PKA). PKA phosphorylates target protein such as hormone-sensitive lipase (HSL) and perilipin 1 (PLIN). PLIN phosphorylation is a key event in the sequential activation of TAG hydrolysis involving adipose triglyceride lipase (ATGL), HSL, and monoglyceride lipase (MGL). During the fed state, insulin, through activation of phosphodiesterase-3B (PDE-3B), inhibits catecholamine-induced lipolysis via the degradation of cAMP.
CLASS       Organismal Systems; Endocrine system
PATHWAY_MAP hsa04923  Regulation of lipolysis in adipocytes
DRUG        D01238  Bucladesine sodium (JAN)
            D02702  Talibegron hydrochloride (USAN)
            D07546  Bucladesine (INN)
DBLINKS     GO: 0016042
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        7252  TSHB; thyroid stimulating hormone subunit beta [KO:K05251]
            1081  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
            7253  TSHR; thyroid stimulating hormone receptor [KO:K04249]
            153  ADRB1; adrenoceptor beta 1 [KO:K04141]
            154  ADRB2; adrenoceptor beta 2 [KO:K04142]
            155  ADRB3; adrenoceptor beta 3 [KO:K04143]
            2778  GNAS; GNAS complex locus [KO:K04632]
            107  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
            108  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
            109  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
            196883  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
            111  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
            112  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
            113  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
            114  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
            115  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
            5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
            5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
            5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
            4878  NPPA; natriuretic peptide A [KO:K12334]
            4881  NPR1; natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
            5592  PRKG1; protein kinase cGMP-dependent 1 [KO:K07376] [EC:2.7.11.12]
            5593  PRKG2; protein kinase cGMP-dependent 2 [KO:K19477] [EC:2.7.11.12]
            5346  PLIN1; perilipin 1 [KO:K08768]
            63924  CIDEC; cell death inducing DFFA like effector c [KO:K25878]
            3991  LIPE; lipase E, hormone sensitive type [KO:K07188] [EC:3.1.1.79]
            57104  PNPLA2; patatin like phospholipase domain containing 2 [KO:K16816] [EC:3.1.1.3]
            51099  ABHD5; abhydrolase domain containing 5, lysophosphatidic acid acyltransferase [KO:K13699] [EC:2.3.1.51]
            11343  MGLL; monoglyceride lipase [KO:K01054] [EC:3.1.1.23]
            2167  FABP4; fatty acid binding protein 4 [KO:K08753]
            364  AQP7; aquaporin 7 [KO:K08771]
            100509620  AQP7B; aquaporin 7B [KO:K08771]
            3630  INS; insulin [KO:K04526]
            3643  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
            3667  IRS1; insulin receptor substrate 1 [KO:K16172]
            8660  IRS2; insulin receptor substrate 2 [KO:K07187]
            8471  IRS4; insulin receptor substrate 4 [KO:K17446]
            5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
            5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
            5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
            5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
            5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
            8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
            207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
            208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
            10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
            5140  PDE3B; phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
            11145  PLAAT3; phospholipase A and acyltransferase 3 [KO:K16817] [EC:3.1.1.32 3.1.1.4]
            54979  PLAAT2; phospholipase A and acyltransferase 2 [KO:K16817] [EC:3.1.1.32 3.1.1.4]
            5742  PTGS1; prostaglandin-endoperoxide synthase 1 [KO:K00509] [EC:1.14.99.1]
            5743  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
            134  ADORA1; adenosine A1 receptor [KO:K04265]
            5733  PTGER3; prostaglandin E receptor 3 [KO:K04260]
            4852  NPY; neuropeptide Y [KO:K05232]
            4886  NPY1R; neuropeptide Y receptor Y1 [KO:K04204]
            2770  GNAI1; G protein subunit alpha i1 [KO:K04630]
            2773  GNAI3; G protein subunit alpha i3 [KO:K04630]
            2771  GNAI2; G protein subunit alpha i2 [KO:K04630]
COMPOUND    C00020  AMP
            C00116  Glycerol
            C00162  Fatty acid
            C00165  Diacylglycerol
            C00212  Adenosine
            C00219  Arachidonate
            C00422  Triacylglycerol
            C00547  L-Noradrenaline
            C00575  3',5'-Cyclic AMP
            C00584  Prostaglandin E2
            C00788  L-Adrenaline
            C00942  3',5'-Cyclic GMP
            C01885  1-Acylglycerol
            C02140  Corticosterone
REFERENCE   PMID:20025992
  AUTHORS   Ahmadian M, Wang Y, Sul HS
  TITLE     Lipolysis in adipocytes.
  JOURNAL   Int J Biochem Cell Biol 42:555-9 (2010)
            DOI:10.1016/j.biocel.2009.12.009
REFERENCE   PMID:19796963
  AUTHORS   Ahmadian M, Duncan RE, Sul HS
  TITLE     The skinny on fat: lipolysis and fatty acid utilization in adipocytes.
  JOURNAL   Trends Endocrinol Metab 20:424-8 (2009)
            DOI:10.1016/j.tem.2009.06.002
REFERENCE   PMID:18762440
  AUTHORS   Wang S, Soni KG, Semache M, Casavant S, Fortier M, Pan L, Mitchell GA
  TITLE     Lipolysis and the integrated physiology of lipid energy metabolism.
  JOURNAL   Mol Genet Metab 95:117-26 (2008)
            DOI:10.1016/j.ymgme.2008.06.012
REFERENCE   PMID:21900692
  AUTHORS   Lafontan M
  TITLE     Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways.
  JOURNAL   Am J Physiol Cell Physiol 302:C327-59 (2012)
            DOI:10.1152/ajpcell.00168.2011
REFERENCE   PMID:24872083
  AUTHORS   Fruhbeck G, Mendez-Gimenez L, Fernandez-Formoso JA, Fernandez S, Rodriguez A
  TITLE     Regulation of adipocyte lipolysis.
  JOURNAL   Nutr Res Rev 27:63-93 (2014)
            DOI:10.1017/S095442241400002X
REFERENCE   PMID:24676492
  AUTHORS   Proenca AR, Sertie RA, Oliveira AC, Campana AB, Caminhotto RO, Chimin P, Lima FB
  TITLE     New concepts in white adipose tissue physiology.
  JOURNAL   Braz J Med Biol Res 47:192-205 (2014)
            DOI:10.1590/1414-431X20132911
REFERENCE   PMID:17313320
  AUTHORS   Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS
  TITLE     Regulation of lipolysis in adipocytes.
  JOURNAL   Annu Rev Nutr 27:79-101 (2007)
            DOI:10.1146/annurev.nutr.27.061406.093734
REFERENCE   PMID:19136990
  AUTHORS   Lafontan M
  TITLE     Advances in adipose tissue metabolism.
  JOURNAL   Int J Obes (Lond) 32 Suppl 7:S39-51 (2008)
            DOI:10.1038/ijo.2008.237
REFERENCE   PMID:17218471
  AUTHORS   Jaworski K, Sarkadi-Nagy E, Duncan RE, Ahmadian M, Sul HS
  TITLE     Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue.
  JOURNAL   Am J Physiol Gastrointest Liver Physiol 293:G1-4 (2007)
            DOI:10.1152/ajpgi.00554.2006
REFERENCE   PMID:22298655
  AUTHORS   Thompson D, Karpe F, Lafontan M, Frayn K
  TITLE     Physical activity and exercise in the regulation of human adipose tissue physiology.
  JOURNAL   Physiol Rev 92:157-91 (2012)
            DOI:10.1152/physrev.00012.2011
REFERENCE   PMID:19464318
  AUTHORS   Lafontan M, Langin D
  TITLE     Lipolysis and lipid mobilization in human adipose tissue.
  JOURNAL   Prog Lipid Res 48:275-97 (2009)
            DOI:10.1016/j.plipres.2009.05.001
REFERENCE   PMID:24731595
  AUTHORS   Arner P, Langin D
  TITLE     Lipolysis in lipid turnover, cancer cachexia, and obesity-induced insulin resistance.
  JOURNAL   Trends Endocrinol Metab 25:255-62 (2014)
            DOI:10.1016/j.tem.2014.03.002
REFERENCE   PMID:17878492
  AUTHORS   Brasaemle DL
  TITLE     Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis.
  JOURNAL   J Lipid Res 48:2547-59 (2007)
            DOI:10.1194/jlr.R700014-JLR200
REFERENCE   PMID:21241784
  AUTHORS   Lampidonis AD, Rogdakis E, Voutsinas GE, Stravopodis DJ
  TITLE     The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis.
  JOURNAL   Gene 477:1-11 (2011)
            DOI:10.1016/j.gene.2011.01.007
REFERENCE   PMID:19375517
  AUTHORS   Bickel PE, Tansey JT, Welte MA
  TITLE     PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores.
  JOURNAL   Biochim Biophys Acta 1791:419-40 (2009)
            DOI:10.1016/j.bbalip.2009.04.002
REFERENCE   PMID:24627478
  AUTHORS   Grahn THM, Kaur R, Yin J, Schweiger M, Sharma VM, Lee MJ, Ido Y, Smas CM, Zechner R, Lass A, Puri V
  TITLE     Fat-specific protein 27 (FSP27) interacts with adipose triglyceride lipase (ATGL) to regulate lipolysis and insulin sensitivity in human adipocytes.
  JOURNAL   J Biol Chem 289:12029-12039 (2014)
            DOI:10.1074/jbc.M113.539890
REL_PATHWAY hsa00561  Glycerolipid metabolism
            hsa00590  Arachidonic acid metabolism
            hsa04022  cGMP-PKG signaling pathway
            hsa04024  cAMP signaling pathway
            hsa04910  Insulin signaling pathway
KO_PATHWAY  ko04923
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