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目的 探究4-羟基壬烯醛(4-HNE)是否通过调节自噬影响脂联素的表达以及相关机制。方法 利用4-HNE/AMPK激动剂/mTOR抑制剂/mRFP-LC3处理脂肪细胞，检测细胞内脂联素以及自噬相关蛋白的表达水平。通过IP检测4-HNE对脂联素泛素化水平的影响。结果 4-HNE抑制细胞内脂联素的表达水平，使LC3II减少，P62增多，细胞内自噬受到抑制。4-HNE抑制AMPK的活性，激活mTOR,AMPK激动剂和mTOR抑制剂能够缓解4-HNE对自噬和脂联素表达水平的抑制作用。4-HNE增加了脂联素的泛素化水平，雷帕霉素能够削弱4-HNE所引起的脂联素泛素化增强作用。结论 4-HNE通过抑制AMPK-mTOR-自噬降低脂联素的表达水平，并通过抑制自噬增强泛素化加速脂联素的降解。
Abstract：Objective The purpose of this study is to investigate whether 4-HNE affects the expression of adiponectin by affecting the role of autophagy and the related mechanisms.Methods Adipocytes were treated with 4-HNE/AMPK activator/mTOR inhibitor/mRFP-LC3,and intracellular adiponectin and expression of various protein molecules related to autophagy were detected.The effect of 4-HNE on the level of adiponectin ubiquitination was detected by IP.Results After 4-HNE was applied to mature differentiated adipocytes, the expression of adiponectin was decreased, LC3II was decreased, P62 was increased, suggesting that 4-HNE inhibited autophagy.4-HNE can inhibit AMPK and activate mTOR,meanwhile AMPK activator and mTOR inhibitor can alleviate the inhibitory effect of 4-HNE on autophagy and adiponectin expression.4-HNE increased the ubiquitination level of adiponectin, while rapamycin can attenuate this effect.Conclusion 4-HNE decreased adiponectin level in adipocytes via inhibiting AMPK-mTOR-autophagy pathway.Furthermore, 4-HNE accelerates the degradation of adiponectin by inhibiting autophagy and activating ubiquitination.
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基本信息:
DOI：10.16695/j.cnki.1006-2947.2025.06.001
中图分类号:R329.2
引用信息:
[1]李秋明,王巍巍,黄翔,等.4-羟基壬烯醛抑制脂肪细胞中脂联素的表达[J].解剖科学进展,2025,31(06):741-744+748.DOI:10.16695/j.cnki.1006-2947.2025.06.001.
基金信息:
国家自然科学基金青年基金(81302420); 黑龙江省留学归国人员科学基金(LC2015028); 黑龙江省博士后科研启动金(LBH-Q15084)