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Abstract Title:

Butyrate protects against high-fat diet-induced atherosclerosis via up-regulating ABCA1 expression in apolipoprotein E-deficiency mice.

Abstract Source:

Br J Pharmacol. 2019 Nov 25. Epub 2019 Nov 25. PMID: 31769014

Abstract Author(s):

Yu Du, Xingxing Li, Chunyan Su, Mei Xi, Xiumin Zhang, Zhibo Jiang, Li Wang, Bin Hong

Article Affiliation:

Yu Du

Abstract:

BACKGROUND AND PURPOSE: The gut microbial metabolite butyrate is closely linked to the modulation of metabolic disease. However, the efficacy and molecular mechanism of butyrate involved in atherosclerosis remain to be identified. Here, the pharmacological benefits and mechanism of butyrate were investigated in high-fat diet-fed ApoEmice after 16 weeks' administration.

EXPERIMENTAL APPROACH: Gut microbiota composition was analysed via 16S rRNA gene sequencing of caecal contents. The pharmacological effects of butyrate on atherosclerosis were evaluated in vivo using the ApoEmice model. Serum samples were analysed for physiological parameters, whereas differentially expressed genes in liver samples were identified by hepatic transcriptome profiling. The proteins involved in reverse cholesterol transport were quantified by Western blot and immunohistochemical staining. Finally, the up-regulatory effects of butyrate on ABCA1 were further evaluated in RAW 264.7 cells, and the potential involvement of Sp1 was evaluated by Sp1 inhibition and silencing.

KEY RESULTS: Oral gavage of butyrate altered microbiota composition and enhanced gut microbial diversity that decreased by HFD. Butyrate treatment significantly inhibited the HFD-induced atherosclerosis as well as hepatic steatosis without changing body weight gain in ApoEmice. Butyrate showed the metabolic effects in the liver through regulation of gene expression involved in lipid/glucose metabolism. Furthermore, ABCA1 was significantly induced by butyrate in vivo, ex vivo and in vitro, and Sp1 pathway was identified as a potential mechanism.

CONCLUSIONS AND IMPLICATIONS: Our results demonstrated that butyrate ameliorates HFD-induced atherosclerosis in ApoEmice via ABCA1-mediated cholesterol efflux in macrophages, which suggesting a promising therapeutic strategy for protecting against atherosclerosis.

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