Caulerpa okamurae extract attenuates inflammatory interaction,regulates glucose metabolism and increases insulin sensitivity in 3T3-L1 adipocytes and RAW 264.7 macrophages

摘要

Objective: To examine whether Caulerpa okamurae ethanolic extract(COE) could inhibit obesitymediated inflammation, improve glucose metabolism and increase insulin sensitivity, using in vitro cell models of RAW 264.7 macrophages and 3 T3-L1 adipocytes.Methods: We cocultured 3 T3-L1 adipocytes in direct contact with lipopolysaccharide-stimulated RAW264.7 macrophages and induced insulin resistance in 3 T3-L1 adipocytes with tumor necrosis factor-a(TNF-a) in the presence or absence of 250 mg/m L of COE. We investigated various markers of inflammation, glucose regulation and insulin sensitivity in these models using Griess reagent to measure nitric oxide(NO) production, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose to measure glucose uptake, Western blot analysis to quantify protein expression and reverse transcriptasepolymerase chain reaction to evaluate m RNA expression.Results: We found that COE(250 mg/m L) significantly inhibited the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages by downregulating NO production, nitric oxide synthase 2 expression and nuclear translocation of nuclear factor-j B. COE also showed similar anti-inflammatory activity in coculture, along with decreased TNF-a, interleukin-6 and monocyte chemoattractant protein m RNA expression. In addition, COE also improved glucose uptake in coculture by upregulating glucose transporter-4(GLUT-4) and adiponectin and reducing serine phosphorylation of insulin receptor substrate-1(IRS1). In the TNF-a-induced insulin resistance model of 3 T3-L1 adipocytes, COE significantly improved both basal and insulin-stimulated glucose uptake, accompanied by phosphorylation of IRS1 at tyrosine 632, phospho-50 adenosine monophosphate-activated protein kinase a and glycogen synthase kinase-3 b(Ser9) as well as upregulation of GLUT-4.Conclusion: Together, these findings suggest that COE has potential to treat or prevent obesity-induced metabolic disorders.