KEGG   PATHWAY: ko04923
Entry
ko04923                     Pathway                                
Name
Regulation of lipolysis in adipocytes
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
ko04923  Regulation of lipolysis in adipocytes
ko04923

Other DBs
GO: 0016042
Orthology
K00509  PTGS1, COX1; prostaglandin-endoperoxide synthase 1 [EC:1.14.99.1]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01054  MGLL; acylglycerol lipase [EC:3.1.1.23]
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04141  ADRB1; adrenergic receptor beta-1
K04142  ADRB2; adrenergic receptor beta-2
K04143  ADRB3; adrenergic receptor beta-3
K04204  NPY1R; neuropeptide Y receptor type 1
K04249  TSHR; thyrotropin receptor
K04260  PTGER3; prostaglandin E receptor 3
K04265  ADORA1; adenosine receptor A1
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04526  INS; insulin
K04527  INSR, CD220; insulin receptor [EC:2.7.10.1]
K04630  GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04632  GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K05232  NPY; neuropeptide Y
K05251  TSHB; thyrotropin subunit beta
K07187  IRS2; insulin receptor substrate 2
K07188  LIPE, HSL; hormone-sensitive lipase [EC:3.1.1.79]
K07376  PRKG1; cGMP-dependent protein kinase 1 [EC:2.7.11.12]
K08041  ADCY1; adenylate cyclase 1 [EC:4.6.1.1]
K08042  ADCY2; adenylate cyclase 2 [EC:4.6.1.1]
K08043  ADCY3; adenylate cyclase 3 [EC:4.6.1.1]
K08044  ADCY4; adenylate cyclase 4 [EC:4.6.1.1]
K08045  ADCY5; adenylate cyclase 5 [EC:4.6.1.1]
K08046  ADCY6; adenylate cyclase 6 [EC:4.6.1.1]
K08047  ADCY7; adenylate cyclase 7 [EC:4.6.1.1]
K08048  ADCY8; adenylate cyclase 8 [EC:4.6.1.1]
K08049  ADCY9; adenylate cyclase 9 [EC:4.6.1.1]
K08522  CGA; glycoprotein hormones alpha chain
K08753  FABP4, aP2; fatty acid-binding protein 4, adipocyte
K08768  PLIN1; perilipin-1
K08771  AQP7; aquaporin-7
K11987  PTGS2, COX2; prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]
K12323  ANPRA, NPR1; atrial natriuretic peptide receptor A [EC:4.6.1.2]
K12334  NPPA; natriuretic peptide A
K13296  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [EC:3.1.4.17]
K13699  ABHD5, CGI-58; abhydrolase domain-containing protein 5 [EC:2.3.1.51]
K16172  IRS1; insulin receptor substrate 1
K16816  PNPLA2, ATGL; patatin-like phospholipase domain-containing protein 2 [EC:3.1.1.3]
K16817  PLA2G16; HRAS-like suppressor 3 [EC:3.1.1.32 3.1.1.4]
K17445  IRS3; insulin receptor substrate 3
K17446  IRS4; insulin receptor substrate 4
K19477  PRKG2; cGMP-dependent protein kinase 2 [EC:2.7.11.12]
K25878  CIDEC; cell death activator CIDE-C
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
ko00561  Glycerolipid metabolism
ko00590  Arachidonic acid metabolism
ko04022  cGMP-PKG signaling pathway
ko04024  cAMP signaling pathway
ko04910  Insulin signaling pathway

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