KEGG   PATHWAY: hsa04920Help
Entry
hsa04920                    Pathway                                

Name
Adipocytokine signaling pathway - Homo sapiens (human)
Description
Increased adipocyte volume and number are positively correlated with leptin production, and negatively correlated with production of adiponectin.
Leptin is an important regulator of energy intake and metabolic rate primarily by acting at hypothalamic nuclei. Leptin exerts its anorectic effects by modulating the levels of neuropeptides such as NPY, AGRP, and alpha-MSH. This leptin action is through the JAK kinase, STAT3 phosphorylation, and nuclear transcriptional effect.
Adiponectin lowers plasma glucose and FFAs. These effects are partly accounted for by adiponectin-induced AMPK activation, which in turn stimulates skeletal muscle fatty acid oxidation and glucose uptake. Furthermore, activation of AMPK by adiponectin suppresses endogenous glucose production, concomitantly with inhibition of PEPCK and G6Pase expression.
The proinflammatory cytokine TNFalpha has been implicated as a link between obesity and insulin resistance. TNFalpha interferes with early steps of insulin signaling. Several data have shown that TNFalpha inhibits IRS1 tyrosine phosphorylation by promoting its serine phosphorylation. Among the serine/threonine kinases activated by TNFalpha, JNK, mTOR and IKK have been shown to be involved in this phosphorylation.
Class
Organismal Systems; Endocrine system
BRITE hierarchy
Pathway map
hsa04920  Adipocytokine signaling pathway
hsa04920

Ortholog table
Disease
H00645  Incontinentia pigmenti
H00666  Peutz-Jeghers syndrome
H00831  Primary dystonia
H00836  GLUT1 deficiency syndrome
H00882  Cocoon syndrome
H00967  Adiponectin deficiency
H01018  Metachondromatosis
H01108  CD36 deficiency
H01154  Wolff-Parkinson-White (WPW) syndrome
H01703  Eating Disorders
H02059  Leptin deficiency
H02060  Leptin receptor deficiency
Drug
D00279  Clofibrate (JP17/USP/INN)
D00334  Gemfibrozil (JAN/USP/INN)
D00565  Fenofibrate (JAN/INN)
D00595  Buformin (USAN/INN)
D00742  Etanercept (USAN/INN)
D00944  Metformin hydrochloride (JP17/USP)
D01208  Aluminum clofibrate (JAN/INN)
D01366  Bezafibrate (JP17/USAN/INN)
D02206  Buformin hydrochloride (JP17)
D02598  Infliximab (USAN/INN)
D03106  Bexarotene (JAN/USAN/INN)
D03441  Certolizumab pegol (USAN/INN)
D03521  Ciprofibrate (USAN/INN)
D04358  Golimumab (USAN/INN)
D04966  Metformin (USAN/INN)
D05014  Metreleptin (USAN/INN)
D05292  Oxfenicine (USAN/INN)
D07187  Etofibrate (INN)
D07436  Afelimomab (INN)
D07724  Magnesium clofibrate (INN)
D08351  Phenformin (BAN)
D08352  Phenformin hydrochloride
D08890  Choline fenofibrate (USAN/INN)
D11208  Elafibranor (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
7124  TNF; tumor necrosis factor [KO:K03156]
7132  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
8717  TRADD; TNFRSF1A associated via death domain [KO:K03171]
7133  TNFRSF1B; TNF receptor superfamily member 1B [KO:K05141]
7186  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
2475  MTOR; mechanistic target of rapamycin kinase [KO:K07203] [EC:2.7.11.1]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
1147  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
8517  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
4792  NFKBIA; NFKB inhibitor alpha [KO:K04734]
4793  NFKBIB; NFKB inhibitor beta [KO:K02581]
4794  NFKBIE; NFKB inhibitor epsilon [KO:K05872]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
9021  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
3667  IRS1; insulin receptor substrate 1 [KO:K16172]
8660  IRS2; insulin receptor substrate 2 [KO:K07187]
8471  IRS4; insulin receptor substrate 4 [KO:K17446]
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]
948  CD36; CD36 molecule [KO:K06259]
23305  ACSL6; acyl-CoA synthetase long chain family member 6 [KO:K01897] [EC:6.2.1.3]
2182  ACSL4; acyl-CoA synthetase long chain family member 4 [KO:K01897] [EC:6.2.1.3]
2180  ACSL1; acyl-CoA synthetase long chain family member 1 [KO:K01897] [EC:6.2.1.3]
51703  ACSL5; acyl-CoA synthetase long chain family member 5 [KO:K01897] [EC:6.2.1.3]
2181  ACSL3; acyl-CoA synthetase long chain family member 3 [KO:K01897] [EC:6.2.1.3]
23205  ACSBG1; acyl-CoA synthetase bubblegum family member 1 [KO:K15013] [EC:6.2.1.3]
81616  ACSBG2; acyl-CoA synthetase bubblegum family member 2 [KO:K15013] [EC:6.2.1.3]
5588  PRKCQ; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
3952  LEP; leptin [KO:K05424]
3953  LEPR; leptin receptor [KO:K05062]
3717  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
6774  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
5443  POMC; proopiomelanocortin [KO:K05228]
5562  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.11]
5563  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.11]
5564  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
5565  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
5571  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
53632  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
51422  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
181  AGRP; agouti related neuropeptide [KO:K05231]
4852  NPY; neuropeptide Y [KO:K05232]
10891  PPARGC1A; PPARG coactivator 1 alpha [KO:K07202]
5105  PCK1; phosphoenolpyruvate carboxykinase 1 [KO:K01596] [EC:4.1.1.32]
5106  PCK2; phosphoenolpyruvate carboxykinase 2, mitochondrial [KO:K01596] [EC:4.1.1.32]
2538  G6PC; glucose-6-phosphatase catalytic subunit [KO:K01084] [EC:3.1.3.9]
57818  G6PC2; glucose-6-phosphatase catalytic subunit 2 [KO:K01084] [EC:3.1.3.9]
92579  G6PC3; glucose-6-phosphatase catalytic subunit 3 [KO:K01084] [EC:3.1.3.9]
5781  PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
5465  PPARA; peroxisome proliferator activated receptor alpha [KO:K07294]
6256  RXRA; retinoid X receptor alpha [KO:K08524]
6257  RXRB; retinoid X receptor beta [KO:K08525]
6258  RXRG; retinoid X receptor gamma [KO:K08526]
9370  ADIPOQ; adiponectin, C1Q and collagen domain containing [KO:K07296]
51094  ADIPOR1; adiponectin receptor 1 [KO:K07297]
79602  ADIPOR2; adiponectin receptor 2 [KO:K07297]
6794  STK11; serine/threonine kinase 11 [KO:K07298] [EC:2.7.11.1]
10645  CAMKK2; calcium/calmodulin dependent protein kinase kinase 2 [KO:K07359] [EC:2.7.11.17]
32  ACACB; acetyl-CoA carboxylase beta [KO:K01946] [EC:2.1.3.15 6.3.4.14 6.4.1.2]
1374  CPT1A; carnitine palmitoyltransferase 1A [KO:K08765] [EC:2.3.1.21]
1375  CPT1B; carnitine palmitoyltransferase 1B [KO:K19523] [EC:2.3.1.21]
126129  CPT1C; carnitine palmitoyltransferase 1C [KO:K19524] [EC:2.3.1.21]
6513  SLC2A1; solute carrier family 2 member 1 [KO:K07299]
6517  SLC2A4; solute carrier family 2 member 4 [KO:K07191]
Compound
C00040  Acyl-CoA
C00083  Malonyl-CoA
C00162  Fatty acid
C00165  Diacylglycerol
C00195  N-Acylsphingosine
C00638  Long-chain fatty acid
C15493  9-cis-Retinoic acid
Reference
  Authors
Gual P, Le Marchand-Brustel Y, Tanti JF.
  Title
Positive and negative regulation of insulin signaling through IRS-1 phosphorylation.
  Journal
Biochimie 87:99-109 (2005)
DOI:10.1016/j.biochi.2004.10.019
Reference
  Authors
Hardie DG, Scott JW, Pan DA, Hudson ER.
  Title
Management of cellular energy by the AMP-activated protein kinase system.
  Journal
FEBS Lett 546:113-20 (2003)
DOI:10.1016/S0014-5793(03)00560-X
Reference
  Authors
Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA.
  Title
The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases.
  Journal
J Biol Chem 280:29060-6 (2005)
DOI:10.1074/jbc.M503824200
Reference
  Authors
Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG.
  Title
Central nervous system control of food intake.
  Journal
Nature 404:661-71 (2000)
DOI:10.1038/35007534
Reference
  Authors
Munzberg H, Myers MG Jr.
  Title
Molecular and anatomical determinants of central leptin resistance.
  Journal
Nat Neurosci 8:566-70 (2005)
DOI:10.1038/nn1454
Reference
  Authors
Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, Spiegelman BM.
  Title
Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction.
  Journal
Nature 423:550-5 (2003)
DOI:10.1038/nature01667
Reference
  Authors
Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM.
  Title
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.
  Journal
Nature 413:131-8 (2001)
DOI:10.1038/35093050
Reference
  Authors
Inoue H, Ogawa W, Ozaki M, Haga S, Matsumoto M, Furukawa K, Hashimoto N, Kido Y, Mori T, Sakaue H, Teshigawara K, Jin S, Iguchi H, Hiramatsu R, LeRoith D, Takeda K, Akira S, Kasuga M.
  Title
Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo.
  Journal
Nat Med 10:168-74 (2004)
DOI:10.1038/nm980
Reference
PMID:9671776
  Authors
Zhou YT, Shimabukuro M, Wang MY, Lee Y, Higa M, Milburn JL, Newgard CB, Unger RH.
  Title
Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells.
  Journal
Proc Natl Acad Sci U S A 95:8898-903 (1998)
DOI:10.1073/pnas.95.15.8898
Reference
  Authors
Kelley DE, Mandarino LJ.
  Title
Fuel selection in human skeletal muscle in insulin resistance: a reexamination.
  Journal
Diabetes 49:677-83 (2000)
DOI:10.2337/diabetes.49.5.677
Reference
  Authors
Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T.
  Title
Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.
  Journal
Nat Med 8:1288-95 (2002)
DOI:10.1038/nm788
Reference
  Authors
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T.
  Title
The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.
  Journal
Nat Med 7:941-6 (2001)
DOI:10.1038/90984
Reference
  Authors
Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferre P, Birnbaum MJ, Stuck BJ, Kahn BB.
  Title
AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus.
  Journal
Nature 428:569-74 (2004)
DOI:10.1038/nature02440
Reference
  Authors
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr.
  Title
Obesity is associated with macrophage accumulation in adipose tissue.
  Journal
J Clin Invest 112:1796-808 (2003)
DOI:10.1172/JCI19246
KO pathway
ko04920   

DBGET integrated database retrieval system