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

Jeanne Durendale Chiadak,Jason Perret,Françoise Gregoire,Nargis Bolaky,Valérie Delforge,Tatjana Arsenijevic,Christine Delporte,Kevin Verstrepen,Véronique Flamand

doi:10.1155/2016/1431789

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.

Highlights

In addition to storing excess energy, adipose tissue is widely recognized as an important endocrine organ
As circulating monocyte chemotactic protein-1 (MCP-1) levels are increased in rodent obesity and the role of Forskolin in fat mass reduction is clearly established, the aim of this study was to determine on one hand the expression of MCP-1, TLR4, G-protein coupled receptor 120 (GPR120), β-Arrestin 2, and nuclear factor-κB1 (NFκB1) expression in DC and on the other hand the signaling pathway by which Forskolin affects MCP-1 and GPR120 expression in the LPS-induced inflammatory response in 3T3-L1 cells differentiated into adipocytes
MCP-1, Toll-like receptor-4 (TLR-4), GPR120, and β-Arrestin 2 mRNA levels were measured by RT-qPCR in undifferentiated cells (UDC) and DC

Summary

Introduction

In addition to storing excess energy, adipose tissue is widely recognized as an important endocrine organ. It secretes numerous cytokines called “adipokines” which have various functions, including macrophage recruitment, regulation of feeding behavior, energy homeostasis, and insulin sensitivity [1]. Obesity is characterized by adipose tissue inflammation and macrophage infiltration [2,3,4]. In numerous animal and clinical studies, obesity is associated with a state of low-grade, chronic inflammation in liver and adipose tissue, which includes activation of the innate immune system and the appearance of proinflammatory immune cells [7, 8]. Nutritional strategies designed to alleviate adipokines dysregulation include modulating dietary fatty acids, with the majority of evidence suggesting the antiinflammatory effects of the marine derived long-chain n3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA)

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