A Study Of Gene Expressions Of Toll-like Receptors In Peripheral Blood Mononuclear Cells In Different Fat Acid Tolerance Groups

Objective: This study was conducted to detect gene expressions of Toll-like receptor 2(TLR2)and Toll-like receptor 4(TLR4)in peripheral blood mononuclear cells(PBMCs)and serum C-reactive protein(CRP)and tumor necrosis factor-alpha(TNF-α)levels in different fat acid tolerance groups to explore the association of lipid metabolism and inflammation.Methods:Subjects were recruited from outpatient department of endocrinology in Hebei Province General Hospital during May 2017 to Dec2017.They have signed an in formed consent and took an oral fat tolerance(OFTT).According to TG of fasting level and postprandial level after OFTT at 4h,subjects were divided into 3 groups:normal fat tolerance group(NFT group,0h TG<1.7 mmol/L and 4h TG<2.5 mmol/L),impaired fat tolerance group(IFT group,0h TG<1.7 mmol/L and 4h TG≥2.5mmol/L)and hypertriglyceridemia group(HTG group,0h TG≥1.7mmol/L).There were 20 subjects in NFT group,23 in IFT group and 25 in HTG group.Blood samples were collected at fasting and 4h after high-fat meal.The mRNA expressions of TLR2 and TLR4,biochemical parameters,free fat acid(FFA),CRP and TNF-αwere detected.All statistical analyses were performed using SPSS 21.0software.Results:1.Compared with the NFT group,weight,body mass index(BMI)and waist cirumference(WC)increased in IFT group and HTG group(P<0.05),and HTG group had higher levels than IFT group(P<0.05).2.Compared with NFT group,the levels of TG(0h TG,4h TG)and ApoB(0h ApoB,4h ApoB),FFA(0h FFA,4h FFA)increased in IFT group and HTG group(P<0.05),espesically HTG group.Compared with the fasting state,the levels of TG,LDL-C and ApoB in the NFT group increased after thehigh-fat meal(P<0.05),the levels of TG,HDL-C,LDL-C,ApoB and FFA at4 h increased in IFT group and HTG group(P<0.05).3.Compared with NFT group,levels of TLR2(0h TLR2,4h TLR2)and TLR4(0hTLR4,4hTLR4)increased significantly in IFT group and HTG group(P<0.01),but there was no statistical difference between IFT group and HTG group.Compared with the fasting state,the levels of TLR2 and TLR4 in PBMCs at 4h in three groups increased significantly(P<0.001).4.Compared with NFT group,serum CRP(0h CRP,4h CRP)and TNF-α(0h TNF-α,4h TNF-α)levels were significantly higher in IFT group and HTG group(P<0.001),but there was no difference between IFT group and HTG group.Compared with the fasting state,there was no significant difference of serum CRP levels at 4h in the three groups,while the TNF-α levels at 4h were significantly higher in the three groups(P<0.01).5.TLR2 level in PBMCs was positively correlated with the levels of TG,FFA,CRP and TNF-α in fasting(P<0.05).The results showed the expression levels of 0h TLR2 was positively associated with 0h TLR4 and 4h TLR2(P<0.001).The expression of TLR2 at 4h were positively correlated with TG,FFA,TLR4 and CRPat 4h(P<0.05),which were significantly positively correlated with 0h TLR4 and 4h TNF-α(P<0.001).TLR4 level in PBMCs was positively correlated with the levels of BMI,FBG,TG,HDL-C,LDL-C,ApoA1,ApoB,FFA,TNF-α in fasting(P<0.05),which was significantly related to the expression levels of 0h TLR2 and 4h TLR4(P<0.001).There was a positive correlation between 4hTLR4 expression and 4h TLR2(P<0.05).And TLR4 at 4h was positively correlated with 0h TLR4,4h FFA and 4h TNF-α(P<0.001).Conclusion:1.The gene expressions of TLR2 and TLR4 in PBMCs and the levels of serum CRP and TNF-α increased significantly in patients with impaired lipid tolerance and hypertriglyceridemia,especially after a high-fat meal.2.TLR2 and TLR4 in PBMCs were positively associated with FFA.