Issue Archive

Short-chain fatty acid butyrate acid attenuates atherosclerotic plaque formation in apolipoprotein E-knockout mice and the underlying mechanism

BAI Hong-Bo¹, YANG Ping², ZHANG Han-Bin², LIU Yu-Lin², FANG Shu-Xiang², XU Xiao-Yang^1,*

¹Department of Physiology, School of Basic Medical Science, Guangzhou Medical University, Guangzhou 511436, China；²The Second Clinical School of Guangzhou Medical University, Guangzhou 510260, China

Abstract

This study was designed to evaluate the role of short-chain fatty acid butyrate acid on intestinal morphology and function, and atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE−/−) mice. ApoE−/− mice on high-fat, high-cholesterol diet were treated with butyrate acid (200 mmol/L) or NaCl (control) in the drinking water for 12 weeks, followed by histological evaluations of atherosclerotic lesion in aorta. Real-time PCR analysis and ELISA were used to measure the expression levels of proinflammatory cytokines. Butyrate acid significantly attenuated high-fat, high-cholesterol diet-induced atherosclerotic plaque formation in ApoE−/− mice. Butyrate acid prevented high-fat, high-cholesterol diet-induced inflammation in both the aorta and the circulation, as evidenced by reduced expression of proinflammatory cytokines. These changes were accompanied by a marked attenuation in metabolic endotoxemia lipopolysaccharide (LPS). Butyrate acid induced intestinal expression of the tight junction proteins (Occludin and zona occuldens protein-1), thereby preventing the gut permeability. Butyrate acid dose-dependently upregulated the expression of the tight junction proteins in Caco-2 cells in GPR41-dependent manner. In conclusion, butyrate acid attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier. 

Key words: short-chain fatty acid; butyrate acid; atherosclerosis; gut permeability

Received: 2020-03-13　　Accepted: 2020-08-28

Corresponding author: 许小洋　　E-mail: xiaoyang-xu@gzhmu.edu.cn

DOI: 10.13294/j.aps.2020.0059

Citing This Article：

BAI Hong-Bo, YANG Ping, ZHANG Han-Bin, LIU Yu-Lin, FANG Shu-Xiang, XU Xiao-Yang. Short-chain fatty acid butyrate acid attenuates atherosclerotic plaque formation in apolipoprotein E-knockout mice and the underlying mechanism. Acta Physiol Sin 2021; 73 (1): 42-50 (in Chinese with English abstract).