KEGG   PATHWAY: ko04923Help
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
BRITE hierarchy
Pathway map
ko04923  Regulation of lipolysis in adipocytes
ko04923

Ortholog table
Disease
H00420  Familial partial lipodystrophy
H00736  Dorfman-Chanarin syndrome
H01297  Neutral lipid storage disease with myopathy
H02106  Genetic obesity
Other DBs
GO: 0016042
Orthology
K05251  thyrotropin subunit beta
K08522  glycoprotein hormones alpha chain
K04249  thyrotropin receptor
K04141  adrenergic receptor beta-1
K04142  adrenergic receptor beta-2
K04143  adrenergic receptor beta-3
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K08041  adenylate cyclase 1 [EC:4.6.1.1]
K08042  adenylate cyclase 2 [EC:4.6.1.1]
K08043  adenylate cyclase 3 [EC:4.6.1.1]
K08044  adenylate cyclase 4 [EC:4.6.1.1]
K08045  adenylate cyclase 5 [EC:4.6.1.1]
K08046  adenylate cyclase 6 [EC:4.6.1.1]
K08047  adenylate cyclase 7 [EC:4.6.1.1]
K08048  adenylate cyclase 8 [EC:4.6.1.1]
K08049  adenylate cyclase 9 [EC:4.6.1.1]
K04345  protein kinase A [EC:2.7.11.11]
K12334  natriuretic peptide A
K12323  atrial natriuretic peptide receptor A [EC:4.6.1.2]
K07376  cGMP-dependent protein kinase 1 [EC:2.7.11.12]
K19477  cGMP-dependent protein kinase 2 [EC:2.7.11.12]
K08768  perilipin-1
K07188  hormone-sensitive lipase [EC:3.1.1.79]
K16816  patatin-like phospholipase domain-containing protein 2 [EC:3.1.1.3]
K13699  abhydrolase domain-containing protein 5 [EC:2.3.1.51]
K01054  acylglycerol lipase [EC:3.1.1.23]
K08753  fatty acid-binding protein 4, adipocyte
K08771  aquaporin-7
K04526  insulin
K04527  insulin receptor [EC:2.7.10.1]
K16172  insulin receptor substrate 1
K07187  insulin receptor substrate 2
K17445  insulin receptor substrate 3
K17446  insulin receptor substrate 4
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K13296  cGMP-inhibited 3',5'-cyclic phosphodiesterase B [EC:3.1.4.17]
K16817  HRAS-like suppressor 3 [EC:3.1.1.32 3.1.1.4]
K00509  prostaglandin-endoperoxide synthase 1 [EC:1.14.99.1]
K11987  prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]
K04265  adenosine receptor A1
K04260  prostaglandin E receptor 3
K05232  neuropeptide Y
K04204  neuropeptide Y receptor type 1
K04630  guanine nucleotide-binding protein G(i) subunit alpha
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
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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