Interleukin-27 as a novel player in alleviating hepatic steatosis: Mechanistic insights from an in vitro analysis
Interleukin-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 endopl...
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| Published in: | Biochemical and biophysical research communications Vol. 703; p. 149671 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Elsevier Inc
09-04-2024
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Interleukin-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).
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•IL-27 attenuates palmitate-induced lipid accumulation by improving lipid metabolism in HepG2 cells.•IL-27 suppresses ER stress and apoptosis in palmitate-treated HepG2 cells.•IL-27 enhances AMPK/autophagy signaling.•AMPK/Autophagy pathway supports IL-27 in hepatic lipid deposition, apoptosis by limiting ER stress. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0006-291X 1090-2104 1090-2104 |
| DOI: | 10.1016/j.bbrc.2024.149671 |