KEGG   PATHWAY: map04920Help
Entry
map04920                    Pathway                                

Name
Adipocytokine signaling pathway
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
map04920

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
H01703  
Eating Disorders
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
 

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