A Promising Culture Model for Analyzing the Interaction between Adipose Tissue and Cardiomyocytes
A Promising Culture Model for Analyzing the Interaction between Adipose Tissue and Cardiomyocytes
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DOI：
10.1210/en.2010-1106
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发表时间：
2011-04-01
期刊：
影响因子：
4.8
通讯作者：
Toda, Shuji
中科院分区：
文献类型：
--
作者：
Anan, Mayumi;Uchihashi, Kazuyoshi;Toda, Shuji
心脏具有心外膜脂肪组织，其产生脂肪因子和间充质干细胞。全身脂肪组织参与肥胖相关心脏病的病理生理学。然而，用于分析脂肪组织和心肌细胞之间的直接相互作用的方法尚未建立。在这里，我们展示了新的模型，使用胶原凝胶共培养的脂肪组织片段（ATFs）和HL-1心肌细胞，电子显微镜，免疫组化，实时RT-PCR和ELISA。HL-1细胞在ATF非包埋凝胶上形成复层，而在ATF包埋凝胶上几乎形成单层。ATFs可促进HL-1细胞凋亡、脂质积聚和脂肪酸转运蛋白（FATP）4和CD 36的表达，而ATFs可抑制HL-1细胞生长和肌球蛋白、肌钙蛋白T和心钠素的mRNA表达。Leptin（100 ng/ml）和Adiponectin（10 μ g/ml）处理既不能复制也不能消除ATF诱导的HL-1细胞形态，而FATP 4和CD 36抗体（25 μ g/ml）处理则不能消除这种形态。HL-1细胞增加ATFs中脂联素的产生，而减少瘦素的产生。这些数据表明，我们的模型积极创造脂肪组织HL-1心肌细胞的相互作用，这表明首先，ATFs可能与HL-1细胞的脂毒性通过未知的因素加上FATP 4和CD 36和第二，HL-1细胞可能有助于保持ATFs的静态，影响脂肪因子分泌。该模型可用于研究脂肪组织-心肌细胞的相互作用以及肥胖相关的脂毒性和心脏疾病的机制。（内分泌学152：1599-1605，2011）
The heart has epicardial adipose tissue that produces adipokines and mesenchymal stem cells. Systemic adipose tissue is involved in the pathophysiology of obesity-related heart diseases. However, the method for analyzing the direct interaction between adipose tissue and cardiomyocytes has not been established. Here we show the novel model, using collagen gel coculture of adipose tissue fragments (ATFs) and HL-1 cardiomyocytes, and electron microscopy, immunohistochemistry, real-time RT-PCR, and ELISA. HL-1 cells formed a stratified layer on ATF-nonembedded gel, whereas they formed almost a monolayer on ATF-embedded gel. ATFs promoted the apoptosis, lipid accumulation, and fatty acid transport protein (FATP) expression of FATP4 and CD36 in HL-1 cells, whereas ATFs inhibited the growth and mRNA expression of myosin, troponin T, and atrial natriuretic peptide. Treatment of leptin (100 ng/ml) and adiponectin (10 mu g/ml) neither replicated nor abolished the ATF-induced morphology of HL-1 cells, whereas that of FATP4 and CD36 antibodies (25 mu g/ml) never abolished it. HL-1 cells prohibited the development of CD44+/CD105+ mesenchymal stem cell-like cells and lipid-laden preadipocytes from ATFs. HL-1 cells increased the production of adiponectin in ATFs, whereas they decreased that of leptin. The data indicate that our model actively creates adipose tissue-HL-1 cardiomyocyte interaction, suggesting first that ATFs may be related to the lipotoxiciy of HL-1 cells via unknown factors plus FATP4 and CD36 and second that HL-1 cells may help to retain the static state of ATFs, affecting adipokine secretion. Our model will serve to study adipose tissue-cardiomyocyte interaction and mechanisms of obesity-related lipotoxicity and heart diseases. (Endocrinology 152: 1599-1605, 2011)