KEGG   PATHWAY: pret04920
pret04920                   Pathway                                

Adipocytokine signaling pathway - Poecilia reticulata (guppy)
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.
Organismal Systems; Endocrine system
Pathway map
pret04920  Adipocytokine signaling pathway

Poecilia reticulata (guppy) [GN:pret]
103472136  tumor necrosis factor-like [KO:K03156]
103478006  tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
103462543  tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
103464471  tumor necrosis factor receptor superfamily member 1B-like [KO:K05141]
103469572  TNF receptor-associated factor 2-like isoform X1 [KO:K03173] [EC:]
103473816  TNF receptor-associated factor 2-like isoform X1 [KO:K03173] [EC:]
103473320  TNF receptor-associated factor 2-like [KO:K03173] [EC:]
103467091  mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:]
103473893  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:]
103471253  mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:]
103476945  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
103482024  mapk8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:]
103476976  inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:]
103481753  inhibitor of nuclear factor kappa-B kinase subunit alpha-like isoform X1 [KO:K04467] [EC:]
103470025  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:]
103466941  ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
103457805  NF-kappa-B inhibitor alpha-like [KO:K04734]
103458779  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
103457398  nfkbie; NF-kappa-B inhibitor epsilon [KO:K05872]
103471905  LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit-like [KO:K02580]
103480184  LOW QUALITY PROTEIN: transcription factor p65-like [KO:K04735]
103461355  suppressor of cytokine signaling 3-like [KO:K04696]
103481519  socs3; suppressor of cytokine signaling 3 [KO:K04696]
103480483  insulin receptor substrate 1-B-like [KO:K16172]
103459734  irs2; insulin receptor substrate 2 [KO:K07187]
103476518  insulin receptor substrate 2-like isoform X1 [KO:K07187]
103474601  insulin receptor substrate 2-B-like [KO:K07187]
103480255  insulin receptor substrate 2-B-like [KO:K07187]
103458546  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
103470003  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:]
103474789  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
103476681  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
103459298  platelet glycoprotein 4-like [KO:K06259]
103466187  acsl1; long-chain-fatty-acid--CoA ligase 1 isoform X1 [KO:K01897] [EC:]
103470507  long-chain-fatty-acid--CoA ligase 1-like [KO:K01897] [EC:]
103474928  acsl3; long-chain-fatty-acid--CoA ligase 3 [KO:K01897] [EC:]
103470977  long-chain-fatty-acid--CoA ligase 4-like [KO:K01897] [EC:]
103471009  long-chain-fatty-acid--CoA ligase 1-like isoform X1 [KO:K01897] [EC:]
103475331  long-chain-fatty-acid--CoA ligase 6 isoform X1 [KO:K01897] [EC:]
103479395  long-chain-fatty-acid--CoA ligase 3-like [KO:K01897] [EC:]
103481841  long-chain-fatty-acid--CoA ligase 5 [KO:K01897] [EC:]
103468238  acsbg2; long-chain-fatty-acid--CoA ligase ACSBG2 isoform X1 [KO:K15013] [EC:]
103469930  long-chain-fatty-acid--CoA ligase ACSBG2-like [KO:K15013] [EC:]
103459790  prkcq; protein kinase C theta type isoform X1 [KO:K18052] [EC:]
103459218  LOW QUALITY PROTEIN: leptin-B-like [KO:K05424]
103468503  lepr; leptin receptor [KO:K05062]
103469946  tyrosine-protein kinase JAK2-like [KO:K04447] [EC:]
103473642  jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:]
103469403  stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
103457563  pro-opiomelanocortin-like [KO:K05228]
103472811  pro-opiomelanocortin-like [KO:K05228]
103457138  pomc; pro-opiomelanocortin isoform X1 [KO:K05228]
103473399  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:]
103463785  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:]
103469702  5'-AMP-activated protein kinase subunit beta-1-like [KO:K07199]
103479357  5'-AMP-activated protein kinase subunit beta-2-like [KO:K07199]
103465268  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
103460160  5'-AMP-activated protein kinase subunit gamma-2-like isoform X1 [KO:K07200]
103475605  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
103479581  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
103482256  5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
103460510  agouti-related protein [KO:K05231]
108165703  U13-lycotoxin-Ls1d-like [KO:K05231]
103479079  agouti-signaling protein-like [KO:K05231]
103472228  pro-neuropeptide Y [KO:K05232]
108167040  LOW QUALITY PROTEIN: peptide YY-like [KO:K05232]
103480692  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
103464655  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:]
103482322  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:]
103461716  g6pc2; glucose-6-phosphatase 2 isoform X2 [KO:K01084] [EC:]
103481660  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:]
103481693  g6pc; glucose-6-phosphatase [KO:K01084] [EC:]
103481694  glucose-6-phosphatase-like [KO:K01084] [EC:]
103467098  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:]
103473239  ptpn11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:]
103459501  ppara; peroxisome proliferator-activated receptor alpha [KO:K07294]
103465912  peroxisome proliferator-activated receptor alpha-like [KO:K07294]
103474009  rxra; retinoic acid receptor RXR-alpha [KO:K08524]
103472931  retinoic acid receptor RXR-beta-A isoform X4 [KO:K08525]
103463575  retinoic acid receptor RXR-gamma-B-like isoform X1 [KO:K08526]
103465307  adipor1; adiponectin receptor protein 1 [KO:K07297]
103459286  adiponectin receptor protein 2 [KO:K07297]
103479439  stk11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:]
103473604  calcium/calmodulin-dependent protein kinase kinase 2 [KO:K07359] [EC:]
103470346  acacb; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:]
103466039  cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K08765] [EC:]
103466156  carnitine O-palmitoyltransferase 1, liver isoform-like isoform X1 [KO:K08765] [EC:]
103468298  carnitine O-palmitoyltransferase 1, liver isoform-like [KO:K08765] [EC:]
103481241  carnitine O-palmitoyltransferase 1, liver isoform-like isoform X1 [KO:K08765] [EC:]
103458231  solute carrier family 2, facilitated glucose transporter member 1-like isoform X2 [KO:K07299]
103464733  solute carrier family 2, facilitated glucose transporter member 1-like [KO:K07299]
103466997  solute carrier family 2, facilitated glucose transporter member 1-like [KO:K07299]
103480459  slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
C00040  Acyl-CoA
C00083  Malonyl-CoA
C00162  Fatty acid
C00165  Diacylglycerol
C00195  N-Acylsphingosine
C00638  Long-chain fatty acid
C15493  9-cis-Retinoic acid
Gual P, Le Marchand-Brustel Y, Tanti JF.
Positive and negative regulation of insulin signaling through IRS-1 phosphorylation.
Biochimie 87:99-109 (2005)
Hardie DG, Scott JW, Pan DA, Hudson ER.
Management of cellular energy by the AMP-activated protein kinase system.
FEBS Lett 546:113-20 (2003)
Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA.
The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases.
J Biol Chem 280:29060-6 (2005)
Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG.
Central nervous system control of food intake.
Nature 404:661-71 (2000)
Munzberg H, Myers MG Jr.
Molecular and anatomical determinants of central leptin resistance.
Nat Neurosci 8:566-70 (2005)
Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, Spiegelman BM.
Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction.
Nature 423:550-5 (2003)
Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM.
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.
Nature 413:131-8 (2001)
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.
Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo.
Nat Med 10:168-74 (2004)
Zhou YT, Shimabukuro M, Wang MY, Lee Y, Higa M, Milburn JL, Newgard CB, Unger RH.
Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells.
Proc Natl Acad Sci U S A 95:8898-903 (1998)
Kelley DE, Mandarino LJ.
Fuel selection in human skeletal muscle in insulin resistance: a reexamination.
Diabetes 49:677-83 (2000)
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.
Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.
Nat Med 8:1288-95 (2002)
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.
The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.
Nat Med 7:941-6 (2001)
Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferre P, Birnbaum MJ, Stuck BJ, Kahn BB.
AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus.
Nature 428:569-74 (2004)
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr.
Obesity is associated with macrophage accumulation in adipose tissue.
J Clin Invest 112:1796-808 (2003)
pret04010  MAPK signaling pathway
pret04910  Insulin signaling pathway
KO pathway

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