KEGG   PATHWAY: pret04920
Entry
pret04920                   Pathway                                
Name
Adipocytokine signaling pathway - Poecilia reticulata (guppy)
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
Pathway map
pret04920  Adipocytokine signaling pathway
pret04920

Organism
Poecilia reticulata (guppy) [GN:pret]
Gene
103457138  pomc; pro-opiomelanocortin isoform X1 [KO:K05228]
103457398  nfkbie; NF-kappa-B inhibitor epsilon [KO:K05872]
103457563  [KO:K05228]
103457805  [KO:K04734]
103458231  [KO:K07299]
103458546  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103458779  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
103459218  [KO:K05424]
103459286  [KO:K07297]
103459298  [KO:K06259]
103459501  ppara; peroxisome proliferator-activated receptor alpha [KO:K07294]
103459734  irs2; insulin receptor substrate 2 [KO:K07187]
103459790  prkcq; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
103460160  [KO:K07200]
103460510  [KO:K05231]
103461355  [KO:K04696]
103461716  g6pc2; glucose-6-phosphatase 2 isoform X2 [KO:K01084] [EC:3.1.3.9]
103462543  tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
103463575  [KO:K08526]
103463785  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
103464350  appl1; DCC-interacting protein 13-alpha [KO:K08733]
103464471  [KO:K05141]
103464655  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
103464733  [KO:K07299]
103465268  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
103465307  adipor1; adiponectin receptor protein 1 [KO:K07297]
103465912  [KO:K07294]
103466039  cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K08765] [EC:2.3.1.21]
103466156  [KO:K08765] [EC:2.3.1.21]
103466187  acsl1; long-chain-fatty-acid--CoA ligase 1 isoform X1 [KO:K01897] [EC:6.2.1.3]
103466941  ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
103466997  [KO:K07299]
103467091  mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
103467098  [KO:K07293] [EC:3.1.3.48]
103468238  acsbg2; long-chain-fatty-acid--CoA ligase ACSBG2 isoform X1 [KO:K15013] [EC:6.2.1.3]
103468298  [KO:K08765] [EC:2.3.1.21]
103468503  lepr; leptin receptor [KO:K05062]
103469403  stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
103469572  [KO:K03173] [EC:2.3.2.27]
103469702  [KO:K07199]
103469930  [KO:K15013] [EC:6.2.1.3]
103469946  [KO:K04447] [EC:2.7.10.2]
103470003  [KO:K04456] [EC:2.7.11.1]
103470025  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103470346  acacb; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
103470507  [KO:K01897] [EC:6.2.1.3]
103470977  [KO:K01897] [EC:6.2.1.3]
103471009  [KO:K01897] [EC:6.2.1.3]
103471253  [KO:K04440] [EC:2.7.11.24]
103471905  [KO:K02580]
103472136  [KO:K03156]
103472228  [KO:K05232]
103472811  [KO:K05228]
103472931  [KO:K08525]
103473239  ptpn11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
103473320  [KO:K03173] [EC:2.3.2.27]
103473399  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
103473604  [KO:K07359] [EC:2.7.11.17]
103473642  jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
103473816  [KO:K03173] [EC:2.3.2.27]
103473893  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103474009  rxra; retinoic acid receptor RXR-alpha [KO:K08524]
103474601  [KO:K07187]
103474789  [KO:K04456] [EC:2.7.11.1]
103474928  acsl3; long-chain-fatty-acid--CoA ligase 3 [KO:K01897] [EC:6.2.1.3]
103475331  [KO:K01897] [EC:6.2.1.3]
103475605  [KO:K07200]
103476518  [KO:K07187]
103476681  [KO:K04456] [EC:2.7.11.1]
103476945  [KO:K04440] [EC:2.7.11.24]
103476976  [KO:K04467] [EC:2.7.11.10]
103478006  tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
103478548  [KO:K08524]
103479079  [KO:K05231]
103479357  [KO:K07199]
103479395  [KO:K01897] [EC:6.2.1.3]
103479439  stk11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
103479581  [KO:K07200]
103480184  [KO:K04735]
103480255  [KO:K07187]
103480459  slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
103480483  [KO:K16172]
103480692  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
103481241  [KO:K08765] [EC:2.3.1.21]
103481519  socs3; suppressor of cytokine signaling 3 [KO:K04696]
103481660  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
103481693  g6pc; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
103481694  [KO:K01084] [EC:3.1.3.9]
103481753  [KO:K04467] [EC:2.7.11.10]
103481841  [KO:K01897] [EC:6.2.1.3]
103482024  mapk8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
103482256  [KO:K07200]
103482322  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
108165703  [KO:K05231]
108167040  [KO:K05232]
Compound
C00040  Acyl-CoA
C00076  Calcium cation
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
Related
pathway
pret04010  MAPK signaling pathway
pret04910  Insulin signaling pathway
KO pathway
ko04920   

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