Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NFκB

Mediators Inflamm. 2016:2016:1431789. doi: 10.1155/2016/1431789. Epub 2016 Nov 2.

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.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism*
  • Animals
  • Blotting, Western
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Colforsin / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Lipopolysaccharides / pharmacology*
  • Mice
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • beta-Arrestin 2 / genetics
  • beta-Arrestin 2 / metabolism

Substances

  • Chemokine CCL2
  • FFAR4 protein, mouse
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Toll-Like Receptor 4
  • beta-Arrestin 2
  • Colforsin