Cho, WonjunOh, HeeseungAbd El-Aty, A. M.Ozten, OmerJeong, Ji HoonJung, Tae Woo2024-10-042024-10-0420240006-291X1090-2104https://doi.org/10.1016/j.bbrc.2024.149671http://hdl.handle.net/20.500.12403/3402Interleukin-27 (IL -27) is a recently discovered cytokine that has been implicated in inflammatory and metabolic conditions, such as atherosclerosis and insulin resistance. However, the mechanisms by which IL -27 attenuates hepatic lipid accumulation in hyperlipidemic conditions and counteracts endoplasmic reticulum (ER) stress, a known risk factor for impaired hepatic lipid metabolism, have not been elucidated. This in vitro study was designed to examine the effect of IL -27 on hepatic lipid metabolism. The study included the evaluation of lipogenesis-associated proteins and ER stress markers by Western blotting, the determination of hepatic lipid accumulation by Oil Red O staining, and the examination of autophagosome formation by MDC staining. The results showed that IL -27 treatment reduced lipogenic lipid deposition and the expression of ER stress markers in cultured hepatocytes exposed to palmitate. Moreover, treatment with IL -27 suppressed CD36 expression and enhanced fatty acid oxidation in palmitate-treated hepatocytes. The effects of IL -27 on hyperlipidemic hepatocytes were attenuated when adenosine monophosphate-activated protein kinase (AMPK) or 3-methyladenine (3 MA) were inhibited by small interfering RNA (siRNA). These results suggest that IL -27 attenuates hepatic ER stress and fatty acid uptake and stimulates fatty acid oxidation via AMPK/autophagy signaling, thereby alleviating hepatic steatosis. In conclusion, this study identified IL -27 as a promising therapeutic target for nonalcoholic fatty liver disease (NAFLD).eninfo:eu-repo/semantics/closedAccessIL-27NAFLDER stressAMPKAutophagyObesityArticle70310.1016/j.bbrc.2024.149671383675152-s2.0-85185529828Q1WOS:001188494300001N/A