The effects of dietary linoleic acid on reducing serum cholesterol and atherosclerosis development are nullified by a high-cholesterol diet in male and female apoE-deficient mice

• Published in: British journal of nutrition Vol. 129; no. 5; pp. 737 - 744
• Main Authors: Yuan, Xingyu, Nagamine, Rika, Tanaka, Yasutake, Tsai, Wei-Ting, Jiang, Zhe, Takeyama, Ai, Imaizumi, Katsumi, Sato, Masao
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 14-03-2023
• Subjects: Animals; Aorta; Apolipoprotein E; Apolipoproteins E - genetics; Arteriosclerosis; Atherosclerosis; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Biomarkers; Cholesterol; Cholesterol, Dietary; Coronary vessels; Diet; Dietary intake; Enzymes; Fatty acids; Female; Females; Food intake; Gene expression; High cholesterol diet; Hypercholesterolemia; Hyperlipidemia; Inflammation; Laboratories; Lesions; Linoleic acid; Linoleic Acid - pharmacology; Liver; Male; Males; Metabolism and Metabolic Studies; Mice; Monocyte chemoattractant protein 1; mRNA; Oils & fats; RNA, Messenger; ApoE-deficient mice; Pro-inflammation; Cholesterol; Atherosclerosis; Linoleic acid
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114522001325

Linoleic acid (LA) has a two-sided effect with regard to serum cholesterol-lowering and pro-inflammation, although whether this fatty acid reduces serum cholesterol and the development of atherosclerosis under high-cholesterol conditions has yet to be ascertained. In this study, we examine the effects of dietary LA on reducing serum cholesterol and atherosclerosis development under high-cholesterol conditions. Male and female apoE-deficient (ApoE-/-) mice were fed AIN-76-based diets containing 10% SFA and 0·04 % cholesterol, 10% LA and 0·04% low cholesterol (LALC), or 10% LA and 0·1% high cholesterol (LAHC) for 9 weeks. The results revealed significant reduction in serum cholesterol levels and aortic lesions with increasing levels of pro-inflammatory biomarkers (urinary isoprostane and aortic MCP-1 mRNA) in male and female LALC groups compared with those in the SFA groups (P < 0·05). Furthermore, whereas there were significant increases in the serum cholesterol levels and aortic lesions (P < 0·05), there was no difference in aortic MCP-1 mRNA levels in male and female LAHC groups compared with those in the LALC groups. A high-dietary intake of cholesterol eliminated the serum cholesterol-lowering activity of LA but had no significant effect on aortic inflammation in either male or female ApoE-/- mice. The inhibitory effect of LA on arteriosclerosis is cancelled by a high-cholesterol diet due to a direct increase in serum cholesterol levels. Accordingly, serum cholesterol levels might represent a more prominent pathogenic factor than aortic inflammation in promoting the development of atherosclerosis.