【Animal Modeling】-Study on the alleviation of exercise via FoxO1-lipophagy pathway. Study on hyperlipidemia in ApoE-/- mice

  Objective Lipophagy is a selective autophagy targeting adipose and is regulated by FoxO1. As an effective means of regulating lipid metabolism disorders, there is no report on whether exercise is related to FoxO1-lipophagy process in hyperlipidemia. In this study, two types of exercise were used to intervene in hyperlipidemia model mice, and the changes in adipophagy-related indexes in adipose tissue were detected to explore the possible mechanism of exercise alleviating hyperlipidemia.

  Methods C57BL/6J mice were selected as wild-type control group (WT group); apolipoprotein E knockout (ApoE- /- ) mice were used to construct hyperlipidemia models, which were divided into quiet control group (CON group), moderate intensity The continuous exercise group (MICT group) and the high-intensity intermittent exercise group (HIIT group) were intervened for 6 weeks. The blood lipid levels of mice in each group were detected, and the morphology of adipocytes was observed by HE staining. RT-qPCR and Western Blot were used to detect PI3K, Akt Changes in /p-Akt, FoxO1 /p-FoxO1 and autophagy-related indicators (Beclin1, Atg7, LC3, p62, Rab7).

  Results (1) Compared with the WT group, the plasma levels of TG, TC and LDL-C in the CON group were significantly increased, and the levels of TG and TC in the exercise groups were significantly lower than those in the CON group (P<0.01). (2) HE staining showed that the number of adipocytes in the CON group was increased compared with the WT group in the same field of view (P<0.01). (3) Compared with the WT group, the CON group increased the mRNA expressions of FoxO1, Beclin1, Atg7, LC3 and Rab7, while the PI3K, p-Akt/Akt, p-FoxO1/FoxO1 and P62 expressions decreased (P<0.01), Beclin1, Atg7 , LC3 and Rab7 protein contents increased (P<0.01); the mRNA expressions of FoxO1, Beclin1, LC3, Atg7 and Rab7 in MICT group and HIIT group were lower than those in CON group, PI3K, p-Akt/Akt, p-FoxO1/FoxO1 and The protein content of p62 increased (P<0.05) or (P<0.01), and the protein content of Beclin1, Atg7, LC3, Rab7 decreased (P<0.05) or (P<0.01).

  Conclusion The above results indicate that both MICT and HIIT can regulate blood lipid levels and improve hyperlipidemia by inhibiting the FoxO1-lipophagy pathway of adipocytes.