Adipocytokine signaling pathway - Homo sapiens (human)

Curator(s): Peter D'Adamo

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.    
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Adipocytokine signaling pathway - Homo sapiens (human) cluster_MEMBRANE MEMBRANE cluster_NUCLEUS NUCLEUS cluster_node30 !1 cluster_node31 AGRP/NPY NEURON cluster_node32 POM/CART NEURON cluster_node33 !3 cluster_node34 !2 cluster_MITOCHONDRIA MITOCHONDRIA node1 22 TNFa TNFa->node1 TNFa TNFR1 TNFa->TNFR1 TNFR2 TNFa->TNFR2 TNFRSF1A-associated via death domain TRADD TNF receptor-associated factor 2 TRAF2 TRADD->TRAF2 mechanistic target of rapamycin (serine/threonine kinase) MTOR TRAF2->MTOR JNK TRAF2->JNK IKK TRAF2->IKK node2 20 MTOR->node2 MTOR IRS MTOR->IRS serine phosphorylation node3 11 JNK->node3 JNK JNK->IRS serine phosphorylation node4 8 IKK->node4 IKK IKB IKK->IKB p+ IKK->IRS serine phosphorylation node5 4 IKB->node5 IKB NFKB IKB->NFKB node6 32 suppressor of cytokine signaling 3 SOCS3 JAK SOCS3->JAK FFL SOCS3->IRS leptin receptor LEPR SOCS3->LEPR FFL node7 4 node8 ↓ Glucose uptake Insulin Signaling Pathways node8->Insulin Signaling Pathways Insulin Resistance node8->Insulin Resistance PKC8 PKC8->JNK node9 29 Ceramide AKT Ceramide->AKT DAG DAG->PKC8 node10 Acyl-CoA node10->Ceramide node10->DAG node26 CPT-1 node10->node26 FACS FACS->node10 FATCD36 FATCD36->FACS Free fatty acids Free fatty acids->FATCD36 node11 1 node12 6 leptin LEP LEP->node12 LEP LEP->LEPR node13 2 JAK->node13 JAK signal transducer and activator of transcription 3 (acute-phase response factor) STAT3 JAK->STAT3 P+ node15 SHP-2 JAK->node15 node14 2 STAT3->node14 STAT3 DNA replication helicase 2 homolog (yeast) DNA2 STAT3->DNA2 Growth and reproduction node15->Growth and reproduction node16 4 node17 PGC-1a node17->node16 PGC-1a node18 16 AMPK AMPK->node18 AMPK node22 GLUT1/4 AMPK->node22 ACC2 AMPK->ACC2 agouti related protein homolog (mouse) AGRP AMPK->AGRP FFL neuropeptide Y NPY AMPK->NPY FFL glucose-6-phosphatase,catalytic subunit G6PC AMPK->G6PC FFL PEPCK AMPK->PEPCK FFL MAPK Signaling Pathway Growth and reproduction->MAPK Signaling Pathway node20 6 adiponectin,C1Q and collagen domain containing ADIPOQ ADIPOQ->node20 ADIPOQ ADIPOR ADIPOQ->ADIPOR AMPKK AMPKK->AMPK node21 8 node22->node21 GLUT1/4 node27 ↑ Glucose uptake node22->node27 node25 Malonyl-CoA ACC2->node25 node23 1 Retinoic Acid RXR Retinoic Acid->RXR Long chain fatty acids Long chain fatty acids->RXR node24 4 node25->node26 Calorie restriction Calorie restriction->Insulin Resistance node28 ↑ Energy expenditure node28->Insulin Resistance node29 ↑ Peroxisome node29->Insulin Resistance Fatty acid metabolism ADIPOR->AMPKK peroxisome proliferator-activated receptor alpha PPARA ADIPOR->PPARA ADIPOR->RXR PPARA->node24 PPARA DNA3 PPARA->DNA3 RXR->node23 RXR RXR->DNA3 AGRP->Calorie restriction AGRP->node28 AGRP->NPY FFL AKT->Insulin Signaling Pathways AKT->node9 AKT PEPCK->G6PC FFL Beta oxidation Beta oxidation->Insulin Resistance DNA DNA->SOCS3 DNA->node8 DNA2->node17 DNA2->AMPK node19 a-MSH DNA2->node19 DNA3->node29 DNA3->Fatty acid metabolism DNA3->node26 NFKB->node6 NFKB NFKB->DNA IRS->node7 IRS LEPR->node11 LEPR LEPR->JAK FFL LEPR->PPARA LEPR->RXR TNFR1->TRADD TNFR2->TRAF2 print "