The PI3K/Akt/mTOR signaling pathway regulates lipid metabolism mediated by endoplasmic reticulum stress in goose primary hepatocytes

Abstract

Abstract We have previously demonstrated that the PI3K/Akt/mTOR signaling pathway was closely linked to the lipid metabolism homeostasis in goose primary hepatocytes. Recently, it was demonstrated that endoplasmic reticulum stress (ERS) can not only affect lipogenesis, but also is related to the PI3K/Akt/mTOR signaling pathway, so it was hypothesised that ERS can affect the lipid metabolism through the PI3K/Akt/mTOR signaling pathway. The ERS model was established by treating goose primary hepatocytes with tunicamycin (TM), and then incubated with PI3K/Akt/mTOR signaling pathway inhibitors LY294002 (LY), Rapamycin (Ra) or NVP-BEZ235 (NVP). Hepatocytes were assigned into 5 groups, including control group, TM group, TM+LY group, TM+Ra group, and TM+NVP group. The results showed that compared with the control group, the mRNA expression and the protein content of BIP/GRP78 significantly increased ( P<Â 0.05) in the TM group, indicating that the ERS model was established successfully. The result of Oil Red O staining revealed that TM caused an increase ( P<Â 0.05) in lipid accumulation and in the mRNA expression of PI3K and S6K, implying that ERS could activate the PI3K/Akt/mTOR signaling pathway. Compared with the TM group, the mRNA expression of genes involved in the PI3K/Akt/mTOR signaling pathway ( PI3K, Akt1, mTOR and S6K), lipogenesis ( ACCα, FAS and SREBP-1), VLDL-TG assembly and secretion ( MTTP, DGAT1 and DGAT2) significantly decreased ( P<Â 0.05) in the TM+LY group, the TM+Ra group, and the TM+NVP group, whereas the protein content of CPT1 and MTTP significantly increased ( P<Â 0.05) in the TM+LY group, the TM+Ra group, and the TM+NVP group. These findings suggest that inhibition of the PI3K/Akt/mTOR signaling pathway can effectively decrease the steatosis mediated by ERS in goose hepatocytes.