title: Globular adiponectin decreases leptin-induced tumor necrosis factor-alpha expression by murine macrophages: involvement of cAMP-PKA and MAPK pathways.
abstract: Several lines of evidence have supported a link between obesity and inflammation. The present study investigated the capacity of leptin and globular adiponectin to affect tumor necrosis factor alpha (TNF-alpha) production in murine peritoneal macrophages. Leptin stimulated TNF-alpha production at mRNA as well as protein levels in a dose- and time-dependent manner. Intracellular cAMP concentration was increased and protein kinase A (PKA) was activated with the treatment of leptin, subsequently downstream MAPK signal proteins, ERK1/2 and p38, were phosphorylated. Specific inhibitors for the signal proteins, Rp cAMPS, H89, PD98059, and U0126, or SB203580, suppressed the signaling pathway and TNF-alpha expression. Although gAd partially increased cAMP concentration and PKA activity, it directly reduced leptin-induced ERK1/2 and p38 MAPK phosphorylation thus inhibiting TNF-alpha production. In conclusion, leptin promotes inflammation by stimulating TNF-alpha production, which is mediated by cAMP-PKA-ERK1/2 and p38 MAPK pathways. gAd inhibited leptin-induced TNF-alpha production through suppressing phosphorylation of ERK1/2 and p38 pathways.
authors.affiliation: Department of Nutrition, School of Public Health, Zhongshan University (Northern Campus), Guangzhou, Guangdong Province, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.forename: Mengjun
authors.initials: M
authors.lastname: Hou
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Huilian
authors.initials: H
authors.lastname: Zhu
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xiao
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Wenhua
authors.initials: W
authors.lastname: Ling
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D000242:Cyclic AMP / Q000276:immunology / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D004347:Drug Interactions; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000276:immunology*; D008297:Male; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
chemical_list: D052242:Adiponectin; D002070:Butadienes; D005419:Flavonoids; D007093:Imidazoles; D007546:Isoquinolines; D020738:Leptin; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one