KEGG PATHWAY: ko04923

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

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

K25878

cell death activator CIDE-C

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

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