KEGG PATHWAY: hsa04923

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

Network

Element

N01708

INS-AKT signaling pathway

Drug

D01238

Bucladesine sodium (JAN)

D02702

Talibegron hydrochloride (USAN)

D07546

Bucladesine (INN)

D12769

Nisotirostide (USAN)

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

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