KEGG   PATHWAY: rno04920Help
Entry
rno04920                    Pathway                                

Name
Adipocytokine signaling pathway - Rattus norvegicus (rat)
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
rno04920

All organismsOrtholog table
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
24835  
Tnf; tumor necrosis factor [KO:K03156]
tumor necrosis factor; K03156 tumor necrosis factor superfamily, member 2 [KO:K03156]
25625  
Tnfrsf1a; tumor necrosis factor receptor superfamily, member 1a [KO:K03158]
246756  
Tradd; TNFRSF1A-associated via death domain [KO:K03171]
156767  
Tnfrsf1b; tumor necrosis factor receptor superfamily, member 1b [KO:K05141]
311786  
Traf2; Tnf receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
56718  
Mtor; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
25272  
Mapk10; mitogen activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
50658  
Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
116554  
Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
309361  
Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
84351  
Ikbkb; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
309295  
Ikbkg; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
25493  
Nfkbia; NFKB inhibitor alpha [KO:K04734]
81525  
Nfkbib; NFKB inhibitor beta [KO:K02581]
316241  
Nfkbie; NFKB inhibitor epsilon [KO:K05872]
81736  
Nfkb1; nuclear factor kappa B subunit 1 [KO:K02580]
309165  
Rela; RELA proto-oncogene, NF-kB subunit [KO:K04735]
89829  
Socs3; suppressor of cytokine signaling 3 [KO:K04696]
25467  
Irs1; insulin receptor substrate 1 [KO:K16172]
29376  
Irs2; insulin receptor substrate 2 [KO:K07187]
84021  
Irs3; insulin receptor substrate 3 [KO:K17445]
315350  
Irs4; insulin receptor substrate 4 [KO:K17446]
24185  
Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
25233  
Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
29414  
Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
29184  
Cd36; CD36 molecule [KO:K06259]
499985  
RGD1565355; similar to fatty acid translocase/CD36 [KO:K06259]
94340  
Acsl5; acyl-CoA synthetase long-chain family member 5 [KO:K01897] [EC:6.2.1.3]
113976  
Acsl4; acyl-CoA synthetase long-chain family member 4 [KO:K01897] [EC:6.2.1.3]
114024  
Acsl3; acyl-CoA synthetase long-chain family member 3 [KO:K01897] [EC:6.2.1.3]
117243  
Acsl6; acyl-CoA synthetase long-chain family member 6 [KO:K01897] [EC:6.2.1.3]
25288  
Acsl1; acyl-CoA synthetase long-chain family member 1 [KO:K01897] [EC:6.2.1.3]
171410  
Acsbg1; acyl-CoA synthetase bubblegum family member 1 [KO:K15013] [EC:6.2.1.3]
301120  
Acsbg2; acyl-CoA synthetase bubblegum family member 2 [KO:K15013] [EC:6.2.1.3]
316124  
similar to gonadotropin-regulated long chain acyl-CoA synthetase; K15013 long-chain-fatty-acid--CoA ligase ACSBG [EC:6.2.1.3] [KO:K15013] [EC:6.2.1.3]
85420  
Prkcq; protein kinase C, theta [KO:K18052] [EC:2.7.11.13]
25608  
Lep; leptin [KO:K05424]
24536  
Lepr; leptin receptor [KO:K05062]
24514  
Jak2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
25125  
Stat3; signal transducer and activator of transcription 3 [KO:K04692]
24664  
Pomc; proopiomelanocortin [KO:K05228]
65248  
Prkaa1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.11]
78975  
Prkaa2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.11]
83803  
Prkab1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
64562  
Prkab2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
25520  
Prkag1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
373545  
Prkag2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
301518  
Prkag3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
25582  
Agrp; agouti related neuropeptide [KO:K05231]
24604  
Npy; neuropeptide Y [KO:K05232]
pro-neuropeptide Y-like; K05232 neuropeptide Y [KO:K05232]
83516  
Ppargc1a; PPARG coactivator 1 alpha [KO:K07202]
362282  
Pck1; phosphoenolpyruvate carboxykinase 1 [KO:K01596] [EC:4.1.1.32]
361042  
Pck2; phosphoenolpyruvate carboxykinase 2 (mitochondrial) [KO:K01596] [EC:4.1.1.32]
25634  
G6pc; glucose-6-phosphatase, catalytic subunit [KO:K01084] [EC:3.1.3.9]
681817  
G6pc2; glucose-6-phosphatase catalytic subunit 2 [KO:K01084] [EC:3.1.3.9]
303565  
G6pc3; glucose 6 phosphatase catalytic subunit 3 [KO:K01084] [EC:3.1.3.9]
25622  
Ptpn11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
25747  
Ppara; peroxisome proliferator activated receptor alpha [KO:K07294]
25271  
Rxra; retinoid X receptor alpha [KO:K08524]
361801  
Rxrb; retinoid X receptor beta [KO:K08525]
83574  
Rxrg; retinoid X receptor gamma [KO:K08526]
246253  
Adipoq; adiponectin, C1Q and collagen domain containing [KO:K07296]
312670  
Adipor2; adiponectin receptor 2 [KO:K07297]
289036  
Adipor1; adiponectin receptor 1 [KO:K07297]
314621  
Stk11; serine/threonine kinase 11 [KO:K07298]
60341  
Camkk1; calcium/calmodulin-dependent protein kinase kinase 1 [KO:K07359] [EC:2.7.11.17]
83506  
Camkk2; calcium/calmodulin-dependent protein kinase kinase 2 [KO:K07359] [EC:2.7.11.17]
116719  
Acacb; acetyl-CoA carboxylase beta [KO:K01946] [EC:6.3.4.14 6.4.1.2]
25757  
Cpt1a; carnitine palmitoyltransferase 1A [KO:K08765] [EC:2.3.1.21]
25756  
Cpt1b; carnitine palmitoyltransferase 1B [KO:K19523] [EC:2.3.1.21]
308579  
Cpt1c; carnitine palmitoyltransferase 1c [KO:K19524] [EC:2.3.1.21]
24778  
Slc2a1; solute carrier family 2 member 1 [KO:K07299]
25139  
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)
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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