To investigate whether butyric acid could alleviate chronic intermittent hypoxia (CIH)-induced lipid formation in human preadipocytes-subcutaneous (HPA-s) through accumulation of human antigen R (HuR) and inactivation of AMP-activated protein kinase (AMPK) pathway, human preadipocytes-subcutaneous (HPA-s) were obtained and divided into 3 groups: CIH group: cells were cultured in a three-gas incubator (10% O2); Butyric acid group: 10 mmol/L butyric acid added into cell culture medium. HuR-siRNA was futher transfected into CIH group for verification the function of HuR. Oil red O was implemented for observation of lipid droplets within cells. CCK8 assay was used for detecting cell viability. TUNEL assay as well as flow cytometry analysis was employed for determining cell apoptosis. Western blotting was used for measurement of protein expression levels. RT-qPCR analysis was used for detecting mRNA expression. CIH treatment increased adipocytes proliferation, while butyric acid inhibited cell proliferation and promoted cell apoptosis. The treatment of butyric acid in CIH group downregulated expression of inflammatory factors and increase cell apoptotic rate. Butyric acid treatment increased HuR expression in both cytoplasm and nucleus and decreased the level of p-AMPK and p-ACC, while transfection of AMPK activator or HuR-siRNA would downregulate HuR expression. Moreover, butyric acid alleviated CIH-induced cell proliferation, lipid formation and inflammatory status and promoted cell apoptosis through regulating related genes including p21, PPARγ, C/EBPa, IL-1β, IL-6, TLR4, caspase-8 and caspase-3. In conclusion, butyric acid could alleviate CIH-induced inflammation, cell proliferation and lipid formation through accumulation of HuR and inactivation of AMPK pathway.
Butyric acid alleviated chronic intermittent hypoxia-induced lipid formation and inflammation through upregulating HuR expression and inactivating AMPK pathways
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MiaoShang Su, Yifan He, Sichen Xue, Jueke Yu, Xikai Ren, Nan Huang, Rukkaiya Abdullahi, Manhuan Xu; Butyric acid alleviated chronic intermittent hypoxia-induced lipid formation and inflammation through upregulating HuR expression and inactivating AMPK pathways. Biosci Rep 2021; BSR20203639. doi: https://doi.org/10.1042/BSR20203639
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