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
Adipocytokine signaling pathway
hsa04920

All organismsOrtholog table
Disease
H00645  
Incontinentia pigmenti
H00666  
Peutz-Jeghers syndrome
H00831  
Primary dystonia
H00836  
GLUT1 deficiency syndrome (GLUT1DS)
H00882  
Cocoon syndrome
H00967  
Adiponectin deficiency
H01018  
Metachondromatosis
H01108  
CD36 deficiency
H01154  
Wolff-Parkinson-White (WPW) syndrome
Drug
D00279  
Clofibrate (JP16/USP/INN)
D00334  
Gemfibrozil (JAN/USP/INN)
D00565  
Fenofibrate (JAN/INN)
D00595  
Buformin (USAN/INN)
D00742  
Etanercept (genetical recombination) (JAN)
D00944  
Metformin hydrochloride (JP16/USP)
D01208  
Aluminum clofibrate (JAN/INN)
D01366  
Bezafibrate (JP16/USAN/INN)
D02206  
Buformin hydrochloride (JP16)
D02598  
Infliximab (genetical recombination) (JAN)
D02815  
Alitretinoin (USAN)
D03106  
Bexarotene (JAN/USAN/INN)
D03441  
Certolizumab pegol (genetical recombination) (JAN)
D03521  
Ciprofibrate (USAN/INN)
D03647  
Dapiclermin (USAN/INN)
D04358  
Golimumab (genetical recombination) (JAN)
D04966  
Metformin (USAN/INN)
D05014  
Mettreleptin (genetical recombination) (JAN)
D05091  
Muraglitazar (USAN/INN)
D05292  
Oxfenicine (USAN/INN)
D06102  
Theofibrate (USAN)
D07187  
Etofibrate (INN)
D07436  
Afelimomab (INN)
D07724  
Magnesium clofibrate (INN)
D08351  
Phenformin (BAN)
D08352  
Phenformin hydrochloride
D08845  
Aleglitazar (USAN)
D08890  
Choline fenofibrate (USAN/INN)
D08949  
Naveglitazar (USAN/INN)
D09350  
Indeglitazar (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
7124  
TNF; tumor necrosis factor [KO:K03156]
7132  
TNFRSF1A; tumor necrosis factor receptor superfamily, member 1A [KO:K03158]
8717  
TRADD; TNFRSF1A-associated via death domain [KO:K03171]
7133  
TNFRSF1B; tumor necrosis factor receptor superfamily, member 1B [KO:K05141]
7186  
TRAF2; TNF receptor-associated factor 2 [KO:K03173]
2475  
MTOR; mechanistic target of rapamycin (serine/threonine kinase) [KO:K07203]
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 kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
4792  
NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4793  
NFKBIB; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta [KO:K02581]
4794  
NFKBIE; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon [KO:K05872]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970  
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A [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; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
948  
CD36; CD36 molecule (thrombospondin receptor) [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 (acute-phase response factor) [KO:K04692]
5443  
POMC; proopiomelanocortin [KO:K05228]
5562  
PRKAA1; protein kinase, AMP-activated, alpha 1 catalytic subunit [KO:K07198] [EC:2.7.11.11]
5563  
PRKAA2; protein kinase, AMP-activated, alpha 2 catalytic subunit [KO:K07198] [EC:2.7.11.11]
5564  
PRKAB1; protein kinase, AMP-activated, beta 1 non-catalytic subunit [KO:K07199]
5565  
PRKAB2; protein kinase, AMP-activated, beta 2 non-catalytic subunit [KO:K07199]
5571  
PRKAG1; protein kinase, AMP-activated, gamma 1 non-catalytic subunit [KO:K07200]
53632  
PRKAG3; protein kinase, AMP-activated, gamma 3 non-catalytic subunit [KO:K07200]
51422  
PRKAG2; protein kinase, AMP-activated, gamma 2 non-catalytic subunit [KO:K07200]
181  
AGRP; agouti related neuropeptide [KO:K05231]
4852  
NPY; neuropeptide Y [KO:K05232]
10891  
PPARGC1A; peroxisome proliferator-activated receptor gamma, coactivator 1 alpha [KO:K07202]
5105  
PCK1; phosphoenolpyruvate carboxykinase 1 (soluble) [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, 2 [KO:K01084] [EC:3.1.3.9]
92579  
G6PC3; glucose 6 phosphatase, catalytic, 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]
84254  
CAMKK1; calcium/calmodulin-dependent protein kinase kinase 1, alpha [KO:K07359] [EC:2.7.11.17]
10645  
CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2, beta [KO:K07359] [EC:2.7.11.17]
1374  
CPT1A; carnitine palmitoyltransferase 1A (liver) [KO:K08765] [EC:2.3.1.21]
1375  
CPT1B; carnitine palmitoyltransferase 1B (muscle) [KO:K08765] [EC:2.3.1.21]
126129  
CPT1C; carnitine palmitoyltransferase 1C [KO:K08765] [EC:2.3.1.21]
6513  
SLC2A1; solute carrier family 2 (facilitated glucose transporter), member 1 [KO:K07299]
6517  
SLC2A4; solute carrier family 2 (facilitated glucose transporter), member 4 [KO:K07191]
32  
ACACB; acetyl-CoA carboxylase beta [KO:K11262] [EC:6.3.4.14 6.4.1.2]
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)
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)
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)
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)
Reference
  Authors
Munzberg H, Myers MG Jr.
  Title
Molecular and anatomical determinants of central leptin resistance.
  Journal
Nat Neurosci 8:566-70 (2005)
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)
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)
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)
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)
Reference
  Authors
Kelley DE, Mandarino LJ.
  Title
Fuel selection in human skeletal muscle in insulin resistance: a reexamination.
  Journal
Diabetes 49:677-83 (2000)
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)
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)
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)
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)
KO pathway
 

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