KEGG   PATHWAY: hsa04923
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
hsa04923

Drug
D01238  Bucladesine sodium (JAN)
D02702  Talibegron hydrochloride (USAN)
D07546  Bucladesine (INN)
Other DBs
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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
Related
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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