Zhang Mingyu, Li Yanhong, Wei Xuehong, Tian Feng, Ouyang Fan, Zhao Shuiping, Liu Ling
Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China; Research Institute of Blood Lipid and Atherosclerosis, Central South University, Changsha, Hunan, PR China; Department of Cardiovascular Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, PR China.
Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China; Research Institute of Blood Lipid and Atherosclerosis, Central South University, Changsha, Hunan, PR China; Department of Cardiovascular Medicine, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, PR China.
Biochem Biophys Res Commun. 2017 Nov 4;493(1):298-305. doi: 10.1016/j.bbrc.2017.09.027. Epub 2017 Sep 9.
Diet-associated obesity is coexisted with postprandial hypertriglyceridemia that indicates increased number of triglyceride-rich lipoproteins (TRL). This study aimed to investigate the effect of postprandial TRL-bound apolipoprotein E (ApoE) on adipogenesis and potential mechanisms. 3T3-L1 cells were cultured with (i) human TRL (h-TRL) with or without insulin, or (ii) TRL from wild type mice (WT-TRL) or ApoE knock-out mice (EKO-TRL) and insulin. The differentiating adipocytes were incubated with different kinds of TRL labeled by red fluorescence and confocal microscopy was performed. Receptor associated protein (RAP), heparin or both were added to inhibit low density lipoprotein receptor family receptors, heparan sulfate proteoglycan or both, respectively. With the aid of insulin, postprandial h-TRL or WT-TRL, instead of EKO-TRL, successfully induced adipogenesis. Confocal microscopy revealed red fluorescence in the differentiating adipocytes treated with h-TRL or WT-TRL, but not with EKO-TRL. RAP markedly reduced red fluorescence within the differentiating adipocytes, while heparin had little impact. The low density lipoprotein receptor related protein 1 protein showed upward trend with the increase of TRL concentrations. Taken together, lipoprotein-bound ApoE was required in both postprandial TRL-induced adipogenesis and TRL endocytosis by the differentiating adipocytes, the latter could be partially through low density lipoprotein receptor family dependent-pathway.
与饮食相关的肥胖与餐后高甘油三酯血症并存，后者表明富含甘油三酯的脂蛋白（TRL）数量增加。本研究旨在探讨餐后TRL结合的载脂蛋白E（ApoE）对脂肪生成的影响及其潜在机制。将3T3-L1细胞与（i）含或不含胰岛素的人TRL（h-TRL），或（ii）来自野生型小鼠的TRL（WT-TRL）或载脂蛋白E基因敲除小鼠的TRL（EKO-TRL）及胰岛素一起培养。将分化中的脂肪细胞与用红色荧光标记的不同种类TRL孵育，并进行共聚焦显微镜检查。分别添加受体相关蛋白（RAP）、肝素或两者以抑制低密度脂蛋白受体家族受体、硫酸乙酰肝素蛋白聚糖或两者。在胰岛素的作用下，餐后h-TRL或WT-TRL而非EKO-TRL成功诱导了脂肪生成。共聚焦显微镜显示，用h-TRL或WT-TRL处理的分化中的脂肪细胞中有红色荧光，而用EKO-TRL处理的则没有。RAP显著降低了分化中的脂肪细胞内的红色荧光，而肝素影响很小。随着TRL浓度的增加，低密度脂蛋白受体相关蛋白1的蛋白呈上升趋势。综上所述，脂蛋白结合的ApoE在餐后TRL诱导的脂肪生成和分化中的脂肪细胞对TRL的内吞作用中均是必需的，后者可能部分通过低密度脂蛋白受体家族依赖性途径实现。
