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Intermittent fasting reduces hypertriglyceridemia and protects against atherosclerosis progression in males and females APOE-/- mice, only under chow diet
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International audience. Background and Aims: Intermittent fasting (IF) has been shown to produce beneficial health effects. Preventing atherosclerosis with IF is promising, yet its therapeutic applicability against preexisting atherosclerosis, diverse nutritional challenges, and gender is unknown. We thus investigated the impact of IF on atherosclerosis development in either males or females apolipoprotein E knockout (apoE-/-) mice fed chow (CD) or high fat (HFD) diet.Methods: and results : 2-month-old males or females mice were randomly assigned to either CD or HFD, and half of the mice in each diet were submitted to an IF regimen (fasting every other day) over a 4-month period.Results: While IF resulted in an overall reduction in food intake in CD and HFD groups, it only protected males against body weight gain when animals were subjected to CD. Furthermore, males and females fed CD maintained their plasma cholesterol and displayed a decrease in plasma triglycerides levels upon IF treatment but these benefits were impaired under HFD feeding. Accordingly, IF regimen markedly decreased atherosclerotic lesions under CD only. Mechanistically, the protective effects of IF were at least mediated by an increase in hepatic expression of SR-BI, ABCA1 and ABCG5/G8 leading to enhanced biliary cholesterol secretion under CD only.Conclusions: Collectively, IF is effective in reducing hyperlipidemia and spontaneous atherosclerosis progression in apoE-/- mice independently of gender. Conversely, IF is detrimental when mice were challenged with HFD which indicates that the effectiveness of IF against atherosclerosis progression might vary according to nutritional behavior.
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