线粒体介导番茄红素改善LPS诱导的3T3-L1前脂肪细胞胰岛素信号转导紊乱分子机制研究  

LYCOPENE ALLEVIATES DYSFUNCTION OF INSULIN SIGNAL TRANSDUCTION VIA ENHANCING MITOCHONDRIAL FUNCTION IN 3T3-L1 PREADIPOCYTES INDUCED EXPOSED TO LIPOPOLYSACCHARIDE

作　　者：李婷 王佳 李梦玲 石东星 路上云 邱服斌 LI Ting;WANG Jia;LI Meng-ling;SHI Dong-xing;LU Shang-yun;QIU Fu-bin(Department of Nutrition and Food Hygiene,School of Public Health,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学公共卫生学院营养与食品卫生学教研室,太原030001

出　　处：《营养学报》2022年第2期188-193,共6页Acta Nutrimenta Sinica

基　　金：国家自然科学基金(No.82103840);山西省应用基础研究面上青年基金(No.20210302124642);山西省高等学校科技创新项目(No.2020L0175);山西省博士启动基金(No.SD1914);山西医科大学博士启动基金(No.XD1914)。

摘　　要：目的 探究番茄红素是否可以抑制脂多糖(lipopolysaccharide, LPS)诱导的3T3-L1前脂肪细胞炎症反应、氧化应激以及胰岛素信号转导紊乱,明确线粒体在其中的介导机制。方法 利用LPS诱导3T3-L1前脂肪细胞发生炎症反应,并通过番茄红素进行干预,之后采用H2DCFDA染色、JC-1染色以及Western blots分析番茄红素对LPS诱导的细胞炎症、活性氧(reactive oxygen species, ROS)积累、胰岛素信号紊乱以及线粒体损伤的改善作用;之后利用寡霉素预先孵育细胞,以抑制线粒体功能,分析线粒体是否可介导番茄红素改善细胞胰岛素信号。结果与LPS组相比,番茄红素可以显著抑制MAPKs信号通路的激活、下调促炎因子COX-2表达,改善细胞炎症反应;可上调抗氧化酶HO-1及NQO-1表达,抑制LPS诱导的ROS积累;番茄红素还促进了IRS-1 Tyr612位点磷酸化及其下游靶基因AKT、GSK3β磷酸化,改善了细胞胰岛素信号转导;且通过增强线粒体膜电势以及促进线粒体呼吸链复合物I-III表达,改善了线粒体功能;用寡霉素预先孵育细胞,发现番茄红素对IRS-1/AKT/GSK3β胰岛素信号通路的调节作用减弱。结论 本研究结果表明番茄红素对线粒体功能的增强可能在其改善细胞胰岛素信号过程中起到一定作用。[营养学报,2022,44(2):188-193]Objective To investigate the contributi of mitochondria to the effects of lycopene(LYC) on inflammatory response, oxidative stress and dysfunction of insulin signal transduction in 3T3-L1 preadipocytes exposed to lipopolysaccharide(LPS). Methods 3T3-L1 preadipocytes were pretreated with LYC for 8 h and then exposed to LPS(1μg/ml) for 12 h. H2DCFDA staining, JC-1 staining and western blots were employed to elucidate the effects of LYC on LPS-induced inflammatory response, oxidative stress, dysfunction of insulin signal transduction and mitochondria damage in 3T3-L1 preadipocytes. To further investigate the underlying connection between mitochondria and insulin signaling,oligomycin, a mitochondrial function inhibitor(suppressing ATP synthesis) was employed. Results Compared with the LPS group, LYC significantly blocked the activation of MAPKs signaling, down-regulated the expression of COX-2, attenuated inflammatory response. LYC decreased the levels of ROS via up-regulating expressions of antioxidant enzymes HO-1 and NQO-1. Moreover, LYC promoted the phosphorylation of IRS-1 Y612, AKT and GSK3β, improved insulin signaling. LYC enhanced mitochondrial function through improving mitochondrial membrane potential and elevating protein expressions of mitochondrial respiratory chain complexes I-III. While, with the existence of oligomycin, the beneficial effects of LYC on the regulation of insulin signaling were partly removed in the LPS-treated cells. Conclusion It is concluded that mitochondria might play an important role in the regulation of LYC on insulin signaling. [ACTA NUTRIMENTA SINICA, 2022, 44(2):188-193]

关 键 词：线粒体功能 胰岛素信号转导 番茄红素 3T3-L1前脂肪细胞 LPS 

分 类 号：R151.2[医药卫生—营养与食品卫生学]