PATHWAY: pret04920
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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
BRITE hierarchy
Pathway map
pret04920
Adipocytokine signaling pathway
Ortholog table
Organism
Poecilia reticulata (guppy) [GN:
pret
]
Gene
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:
2.3.2.27
]
103473816
TNF receptor-associated factor 2-like isoform X1 [KO:
K03173
] [EC:
2.3.2.27
]
103473320
TNF receptor-associated factor 2-like [KO:
K03173
] [EC:
2.3.2.27
]
103467091
mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:
K07203
] [EC:
2.7.11.1
]
103473893
mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:
K04440
] [EC:
2.7.11.24
]
103471253
mitogen-activated protein kinase 9 isoform X2 [KO:
K04440
] [EC:
2.7.11.24
]
103476945
mitogen-activated protein kinase 8 isoform X1 [KO:
K04440
] [EC:
2.7.11.24
]
103482024
mapk8; mitogen-activated protein kinase 8 isoform X2 [KO:
K04440
] [EC:
2.7.11.24
]
103476976
inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:
K04467
] [EC:
2.7.11.10
]
103481753
inhibitor of nuclear factor kappa-B kinase subunit alpha-like isoform X1 [KO:
K04467
] [EC:
2.7.11.10
]
103470025
ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:
K07209
] [EC:
2.7.11.10
]
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:
2.7.11.1
]
103470003
RAC-gamma serine/threonine-protein kinase-like [KO:
K04456
] [EC:
2.7.11.1
]
103474789
RAC-beta serine/threonine-protein kinase [KO:
K04456
] [EC:
2.7.11.1
]
103476681
RAC-gamma serine/threonine-protein kinase [KO:
K04456
] [EC:
2.7.11.1
]
103459298
platelet glycoprotein 4-like [KO:
K06259
]
103466187
acsl1; long-chain-fatty-acid--CoA ligase 1 isoform X1 [KO:
K01897
] [EC:
6.2.1.3
]
103470507
long-chain-fatty-acid--CoA ligase 1-like [KO:
K01897
] [EC:
6.2.1.3
]
103474928
acsl3; long-chain-fatty-acid--CoA ligase 3 [KO:
K01897
] [EC:
6.2.1.3
]
103470977
long-chain-fatty-acid--CoA ligase 4-like [KO:
K01897
] [EC:
6.2.1.3
]
103471009
long-chain-fatty-acid--CoA ligase 1-like isoform X1 [KO:
K01897
] [EC:
6.2.1.3
]
103475331
long-chain-fatty-acid--CoA ligase 6 isoform X1 [KO:
K01897
] [EC:
6.2.1.3
]
103479395
long-chain-fatty-acid--CoA ligase 3-like [KO:
K01897
] [EC:
6.2.1.3
]
103481841
long-chain-fatty-acid--CoA ligase 5 [KO:
K01897
] [EC:
6.2.1.3
]
103468238
acsbg2; long-chain-fatty-acid--CoA ligase ACSBG2 isoform X1 [KO:
K15013
] [EC:
6.2.1.3
]
103469930
long-chain-fatty-acid--CoA ligase ACSBG2-like [KO:
K15013
] [EC:
6.2.1.3
]
103459790
prkcq; protein kinase C theta type isoform X1 [KO:
K18052
] [EC:
2.7.11.13
]
103459218
LOW QUALITY PROTEIN: leptin-B-like [KO:
K05424
]
103468503
lepr; leptin receptor [KO:
K05062
]
103469946
tyrosine-protein kinase JAK2-like [KO:
K04447
] [EC:
2.7.10.2
]
103473642
jak2; tyrosine-protein kinase JAK2 [KO:
K04447
] [EC:
2.7.10.2
]
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:
2.7.11.11
]
103463785
prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:
K07198
] [EC:
2.7.11.11
]
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:
4.1.1.32
]
103482322
pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:
K01596
] [EC:
4.1.1.32
]
103461716
g6pc2; glucose-6-phosphatase 2 isoform X2 [KO:
K01084
] [EC:
3.1.3.9
]
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
glucose-6-phosphatase-like [KO:
K01084
] [EC:
3.1.3.9
]
103467098
tyrosine-protein phosphatase non-receptor type 11-like [KO:
K07293
] [EC:
3.1.3.48
]
103473239
ptpn11; tyrosine-protein phosphatase non-receptor type 11 [KO:
K07293
] [EC:
3.1.3.48
]
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:
2.7.11.1
]
103473604
calcium/calmodulin-dependent protein kinase kinase 2 [KO:
K07359
] [EC:
2.7.11.17
]
103470346
acacb; acetyl-CoA carboxylase 2 isoform X1 [KO:
K01946
] [EC:
6.4.1.2
6.3.4.14
2.1.3.15
]
103466039
cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform [KO:
K08765
] [EC:
2.3.1.21
]
103466156
carnitine O-palmitoyltransferase 1, liver isoform-like isoform X1 [KO:
K08765
] [EC:
2.3.1.21
]
103468298
carnitine O-palmitoyltransferase 1, liver isoform-like [KO:
K08765
] [EC:
2.3.1.21
]
103481241
carnitine O-palmitoyltransferase 1, liver isoform-like isoform X1 [KO:
K08765
] [EC:
2.3.1.21
]
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
]
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
PMID:
15733744
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
PMID:
12829246
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
PMID:
15980064
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
PMID:
10766253
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
PMID:
15856064
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
PMID:
12754525
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
PMID:
11557972
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
PMID:
14716305
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
PMID:
10905472
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
PMID:
12368907
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
PMID:
11479627
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
PMID:
15058305
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
PMID:
14679176
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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