title: Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NFκB.
abstract: In an obese state, Toll-like receptor-4 (TLR-4) upregulates proinflammatory adipokines secretion including monocyte chemotactic protein-1 (MCP-1) in adipose tissue. In contrast, G-protein coupled receptor 120 (GPR120) mediates antiobesity effects. The aim of this study was to determine the signaling pathway by which Forskolin (FK), a cyclic adenosine monophosphate- (cAMP-) promoting agent causing positive changes in body composition in overweight and obese adult men, affects MCP-1 and GPR120 expression during an inflammatory response induced by lipopolysaccharide (LPS) in adipocytes, such as in an obese state. 3T3-L1 cells differentiated into adipocytes (DC) were stimulated with LPS in the absence or presence of FK and inhibitors of TLR-4 and inhibitor of kappa B (IκBα). In DC, LPS increased MCP-1, TLR-4, and nuclear factor-κB1 (NFκB1) mRNA levels, whereas it decreased GPR120 mRNA levels. In DC, FK inhibited the LPS-induced increase in MCP-1, TLR-4, and NFκB1 mRNA levels and the LPS-induced decrease in GPR120 mRNA. BAY11-7082 and CLI-095 abolished these LPS-induced effects. In conclusion, FK inhibits LPS-induced increase in MCP-1 mRNA levels and decrease in GPR120 mRNA levels in adipocytes and may be a potential treatment for inflammation in obesity. Furthermore, TLR-4-induced activation of NFκB may be involved in the LPS-induced regulation of these genes.
authors.affiliation: Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium; Department of Biochemistry, Faculty of Sciences, University of Dschang, Dschang, Cameroon.
authors.forename: Jeanne Durendale
authors.initials: JD
authors.lastname: Chiadak
authors.affiliation: Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Arsenijevic
authors.affiliation: Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Verstrepen
authors.affiliation: Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Gregoire
authors.affiliation: Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Nargis
authors.initials: N
authors.lastname: Bolaky
authors.affiliation: Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Valérie
authors.initials: V
authors.lastname: Delforge
authors.affiliation: Institute for Medical Immunology, Faculty of Medicine, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Flamand
authors.affiliation: Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Jason
authors.identifier: 0000-0001-7161-7604
authors.initials: J
authors.lastname: Perret
authors.affiliation: Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christine
authors.identifier: 0000-0003-0385-5824
authors.initials: C
authors.lastname: Delporte
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D000071560:beta-Arrestin 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; C498007:FFAR4 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D051197:Toll-Like Receptor 4; D000071560:beta-Arrestin 2; D005576:Colforsin