CISD1与人类内脏脂肪组织中肥胖相关的脂肪生成功能障碍有关。
CISD1 in association with obesity-associated dysfunctional adipogenesis in human visceral adipose tissue.
作者信息
Moreno-Navarrete José María, Moreno María, Ortega Francisco, Sabater Mònica, Xifra Gemma, Ricart Wifredo, Fernández-Real José Manuel
机构信息
Department of Diabetes, Endocrinology and Nutrition, Institut D'investigació Biomèdica De Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto De Salud Carlos III (ISCIII), Girona, Spain.
出版信息
Obesity (Silver Spring). 2016 Jan;24(1):139-47. doi: 10.1002/oby.21334.
OBJECTIVE
To investigate CISD1 mRNA and protein in human adipose tissue in association with obesity and adipogenesis.
METHODS
Subcutaneous (SAT) and visceral (VAT) adipose tissue CISD1 gene expression (real-time PCR) and protein (Western blot) levels were investigated in human adipose tissue and during human adipocyte differentiation.
RESULTS
SAT and VAT CISD1 mRNA and protein levels were significantly decreased in subjects with obesity and negatively correlated with BMI after controlling for age and sex. In participants with morbid obesity, VAT CISD1 gene expression was positively correlated with insulin sensitivity (r = 0.47, P = 0.01), and bariatric surgery-induced weight loss led to increased SAT CISD1 mRNA levels. In both VAT and SAT, CISD1 gene expression was significantly associated with SIRT1, ISCA2, and mitochondrial biogenesis-related (PPARGC1A, TFAM, and MT-CO3) and browning-related (PRDM16 and UCP1) gene expression. In addition, VAT CISD1 gene expression was significantly associated with adipogenic and iron metabolism-related genes. Importantly, these correlations were replicated in a second cohort. At the cellular level, CISD1 gene expression increased during human adipocyte differentiation in correlation with adipogenic genes (r > 0.60, P < 0.005).
CONCLUSIONS
These data suggest a possible role of CISD1 in obesity-associated dysfunctional adipogenesis in human VAT.
目的
研究人脂肪组织中CISD1 mRNA和蛋白与肥胖及脂肪生成的关系。
方法
检测人脂肪组织及人脂肪细胞分化过程中皮下脂肪组织（SAT）和内脏脂肪组织（VAT）中CISD1基因表达（实时定量PCR）和蛋白（蛋白质免疫印迹法）水平。
结果
肥胖受试者的SAT和VAT中CISD1 mRNA和蛋白水平显著降低，在控制年龄和性别后与体重指数呈负相关。在病态肥胖参与者中，VAT中CISD1基因表达与胰岛素敏感性呈正相关（r = 0.47，P = 0.01），减重手术引起的体重减轻导致SAT中CISD1 mRNA水平升高。在VAT和SAT中，CISD1基因表达均与沉默调节蛋白1（SIRT1）、铁硫簇组装蛋白2（ISCA2）以及线粒体生物合成相关基因（过氧化物酶体增殖物激活受体γ共激活因子1α（PPARGC1A）、线粒体转录因子A（TFAM）和细胞色素c氧化酶Ⅲ（MT-CO3））和产热相关基因（PR结构域蛋白16（PRDM16）和解偶联蛋白1（UCP1））的表达显著相关。此外，VAT中CISD1基因表达与脂肪生成及铁代谢相关基因显著相关。重要的是，这些相关性在第二个队列中得到了验证。在细胞水平上，人脂肪细胞分化过程中CISD1基因表达增加，与脂肪生成相关基因相关（r > 0.60，P < 0.005）。
结论
这些数据表明CISD1在人VAT中与肥胖相关的脂肪生成功能障碍中可能发挥作用。
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