Caprylic Acid Improves Lipid Metabolism, Suppresses the Inflammatory Response and Activates the ABCA1/p-JAK2/pSTAT3 Signaling Pathway in C57BL/6J Mice and RAW264.7 Cells

Objective This study aimed to investigate the effects of caprylic acid(C8:0)on lipid metabolism and inflammation,and examine the mechanisms underlying these effects in mice and cells.Methods Fifty-six 6-week-old male C57BL/6J mice were randomly allocated to four groups fed a highfat diet(HFD)without or with 2%C8:0,palmitic acid(C16:0)or eicosapentaenoic acid(EPA).RAW246.7 cells were randomly divided into five groups:normal,lipopolysaccharide(LPS),LPS+C8:0,LPS+EPA and LPS+cAMP.The serum lipid profiles,inflammatory biomolecules,and ABCA1 and JAK2/STAT3 mRNA and protein expression were measured.Results C8:0 decreased TC and LDL-C,and increased the HDL-C/LDL-C ratio after injection of LPS.Without LPS,it decreased TC in mice(P<0.05).Moreover,C8:0 decreased the inflammatory response after LPS treatment in both mice and cells(P<0.05).Mechanistic investigations in C57BL/6J mouse aortas after injection of LPS indicated that C8:0 resulted in higher ABCA1 and JAK2/STAT3 expression than that with HFD,C16:0 and EPA,and resulted in lower TNF-α,NF-κB mRNA expression than that with HFD(P<0.05).In RAW 264.7 cells,C8:0 resulted in lower expression of pNF-κBP65 than that in the LPS group,and higher protein expression of ABCA1,p-JAK2 and p-STAT3 than that in the LPS and LPS+cAMP groups(P<0.05).Conclusion Our studies demonstrated that C8:0 may play an important role in lipid metabolism and the inflammatory response,and the mechanism may be associated with ABCA1 and the p-JAK2/p-STAT3 signaling pathway.

Effects of Oxidized Low Density Lipoprotein onthe Expression and Function of ABCA1 in Macrophages

Summary:In the present study, we examined the regulation of the expression and function of ABCA1 by modified LDL (ox-LDL) in vitro. After incubation with apoA-I for 24 h, RAW264.7 cells effluxed 37.65 % cholesterol loaded by acetyl LDL (ac-LDL), and 9.78 % cholesterol in ox-LDL group. The level of ABCA1 mRNA increased about three times either when cells were incubated with 100 μg /mL ac-LDL or with 100 μg /mL ox-LDL. However, the level of ABCA1 protein rose by 1.57 times in ac-LDL group and 1.26 times in ox-LDL group. These results demonstrated that ox-LDL had different effect on the expression and function of ABCA1, ox-LDL might decrease the cholesterol efflux mediated by ABCA1 through other unknown mechanisms.

A new discovered ABCA1 gene polymorphisms and the association of ABCA1 SNPs with coronary artery disease and plasma lipids in Chinese population

Single nucleotide polymorphisms （SNP） of ATP-binding cassette transporter A1 （ABCA1） gene are related to plasma lipid and susceptibility to coronary artery disease （CAD）. Our first goal was to screen all 50 coding regions of ABCA1 to find new SNPs. Our second goal was to investigate the frequency distribution of R1587K and M883I polymorphisms of ABCA1 gene, which are the variant occurred most frequently, in Chinese people and to evaluate their association with the CAD phenotype and plasma lipids. Methods： Single-strand conformation polymorphism （SSCP） and DNA sequence were used for confirming new SNP of ABCA1, and restriction fragment length polymorphism （RFLP） were applied for confirming genotypes of R1587K and M883I in 112 CAD cases and 108 healthy people. Results： We discovered a new ABCA1 SNP in Chinese population, which converse 233 amino acids from Methionine to Valine （M233V）. This new ABCA1 SNP located in exon7, and might potentially modulate the biological function of lipid metabolism. For R1587K and M883I SNPs, the K allele and I allele frequency was 28.9% and 31.1%, respectively. The K allele at R1587K conferred lower mean values of HDL-C in a dose-dependent manner in both CAD patients and healthy people. However, 883I allele was not associated with plasma lipid level. Neither 1587KK nor 883II associated with increased risk of CAD. Conclusion： Our study finds a potential functional ABCA1 SNPs and revealed K allele of R1587K associated decreased HDL-C level in Chinese population.

Effect of Quercetin on Atherosclerosis Based on Expressions of ABCA1, LXR-α and PCSK9 in ApoE-/- Mice

Objective:To investigate the effect of quercetin on ATP binding cassette transporter A1(ABCA1),liver X receptor(LXR),and proprotein convertase subtilisin/kexin type 9(PCSK9)expressions in apoE-knockout(ApoE-/-)mice.Methods:The high-fat diet-induced atherosclerosis(AS)in ApoE-/-mice was established.Thirtysix mice were divided into 3 groups using random number table method:model group(n=12),quercetin group(n=12),and atorvastatin group(n=12),with C57BL/6J mice of the same strain and age as the control group(n=12).Quercetin group and atorvastatin group were administrated with quercetin and atorvastatin by oral gavage,with doses of 12.5 and 4 mg/(kg・d),respectively.Animals in the control and model groups were given an equal volume of distilled water by oral gavage once per day for a total of 12 weeks.Western blot and immunohistochemical methods were employed to determine the aortic ABCA1,LXR-a and PCSK9 protein expressi on.En zyme linked imm uno sorbent assay method was used to detect the expressi on of serum total cholesterol(TC),triglyceride(TG),high density lipoprotein-cholesterol(HDL-C),low density lipoproteincholesterol(LDL-C),tumor necrosis factor-a(TNF-a),interleukin-6(IL-6),and IL-10,combined with tissue pathological exami nation.Results:ApoE-/-mice fed with a high-fat diet had no table atherosclerosis lesions,with reduced ABCA1,LXR-a and IL-10 levels(all P<0.01),elevated PCSK9,TNF-a and IL-6 expression,and increased TC and LDL-C con tents(all P<0.01).After querceti n in terventi on,the areas of AS plaques and the expressions of PCSK9,TNF-a and IL-6 were significantly reduced(all P<0.01),while the expressions of ABCA1 and LXR-a were increased significantly(all P<0.01).Conclusion:Quercetin effectively interfered with AS development by regulating the expressions of ABCA1,LXR-a and PCSK9 in ApoE,mice.