Exercise alleviates hyperlipidemia via the FoxO1-lipophagic signaling pathway in ApoE- / - mice
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1. Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing 100084, China. 2. Sport Science College of Beijing Sport University, Beijing 100084. 3. Sports Department of Northwestern Polytechnical University, Xi’an 710072

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    Abstract:

    Objective Lipophagy is a type of selective autophagy that targets fat and is regulated by FoxO1. Exercise is an effective method to regulate lipid metabolism disorders. Whether the regulation of hyperlipidemia is mediated by the FoxO1-lipophagy pathway remains unreported. In this study, two types of exercise were used as interventions in hyperlipidemia model mice, and the changes in lipophagy-related indexes in adipose tissue were detected to explore the possible mechanism by which exercise alleviates hyperlipidemia. Methods C57BL/ 6J mice were selected as the wild-type control group (WT group). The hyperlipidemia model was constructed by apolipoprotein E gene knockout (ApoE- / - ), and mice were divided into three groups: the silent control group (CON group), moderate-intensity continuous training group (MICT group) and high-intensity intermittent training group (HIIT group). After 6 weeks of intervention, the blood lipid levels in each group were detected, and the morphology of adipocytes was observed by HE staining. The changes in PI3K, Akt / p-Akt, FoxO1 / p-FoxO1 and autophagy-related indexes (Beclin1, Atg7, LC3, p62 and Rab7) in adipose tissue were measured by RT-qPCR and Western Blot. Results (1) Plasma TG, TC and LDL-C levels in the CON group were significantly increased compared with the WT group, and TG and TC levels in the exercise groups were significantly decreased compared with the CON group (P< 0.01). (2) HE staining showed that the number of adipocytes in the CON group were increased, compared with the WT group in the same field (P< 0. 01). (3) Compared with the WT group, the mRNA expression levels of FoxO1, Beclin1, Atg7, LC3 and Rab7 were increased in the CON group, and the expression levels of PI3K, p-Akt / Akt, p-FoxO1 / FoxO1 and P62 were decreased (P< 0.01). In addition, Beclin1, Atg7, LC3 and Rab7 protein contents were increased (P< 0.01). The mRNA levels of FoxO1, Beclin1, LC3, Atg7 and Rab7 in the MICT group and HIIT group were lower than those in the CON group, whereas the protein contents of PI3K, p-Akt / Akt, p- FoxO1 / FoxO1 and p62 were increased (P< 0.05 or P< 0.01). The protein contents of Beclin1, Atg7, LC3 and Rab7 were decreased (P< 0.05 or P< 0.01). Conclusions These Results suggest that both MICT and HIIT alleviate hyperlipidemia by inhibiting of the FoxO1-lipophagic signaling pathway in adipocytes, thereby regulating lipid levels.

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  • Received:June 03,2021
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  • Online: February 17,2022
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