Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA.
Obesity (Silver Spring). 2021 Dec;29(12):2068-2080. doi: 10.1002/oby.23295. Epub 2021 Oct 21.
This study investigated whether variations in cell death-inducing DNA fragmentation factor alpha subunit-like effector A (CIDEA) mRNA expression and protein levels are modulated by the pattern of abdominal fat distribution in adolescent girls with obesity.
This study recruited 35 adolescent girls with obesity and characterized their abdominal fat distribution by magnetic resonance imaging. Participants had only a periumbilical/abdominal (n = 14) or a paired abdominal and gluteal subcutaneous adipose tissue (SAT) biopsy (n = 21). CIDEA expression was determined by reverse transcription-polymerase chain reaction, CIDEA protein level by Western blot, and the turnover of adipose lipids and adipocytes by H O labeling. In six girls, a second abdominal SAT biopsy was performed (after ~34.2 months) to explore the weight gain effect on CIDEA expression in abdominal SAT.
CIDEA expression decreased in abdominal SAT from participants with high visceral adipose tissue (VAT)/(VAT+SAT); CIDEA inversely correlated with number of small adipocytes, with the increase in preadipocyte proliferation, and with adipogenesis. A strong inverse correlation was found between CIDEA protein level with the newly synthetized glycerol (r = -0.839, p = 0.0047). Following weight gain, an increase in adipocytes' cell diameter with a decrease in CIDEA expression and RNA-sequencing transcriptomic profile typical of adipocyte dysfunction was observed.
Reduced expression of CIDEA in girls with high VAT/(VAT+SAT) is associated with adipocyte hypertrophy and insulin resistance.
本研究旨在探讨细胞死亡诱导 DNA 片段化因子α亚单位样效应因子 A(CIDEA)mRNA 表达和蛋白水平的变化是否受肥胖青少年腹部脂肪分布模式的调节。
本研究招募了 35 名肥胖青少年,并通过磁共振成像对其腹部脂肪分布进行了特征描述。参与者仅接受脐周/腹部(n = 14)或腹部和臀部皮下脂肪组织(SAT)的配对活检(n = 21)。通过逆转录-聚合酶链反应确定 CIDEA 表达,通过 Western blot 确定 CIDEA 蛋白水平,通过 H O 标记测定脂肪脂质和脂肪细胞的周转率。在 6 名女孩中,进行了第二次腹部 SAT 活检(约 34.2 个月后),以探讨体重增加对腹部 SAT 中 CIDEA 表达的影响。
高内脏脂肪组织(VAT)/(VAT+SAT)参与者的腹部 SAT 中 CIDEA 表达减少;CIDEA 与小脂肪细胞数量呈负相关,与前脂肪细胞增殖增加和脂肪生成呈负相关。CIDEA 蛋白水平与新合成的甘油呈强烈负相关(r = -0.839,p = 0.0047)。体重增加后,观察到脂肪细胞直径增加,CIDEA 表达和 RNA 测序转录组谱降低,这是脂肪细胞功能障碍的典型特征。
高 VAT/(VAT+SAT)的女孩中 CIDEA 表达降低与脂肪细胞肥大和胰岛素抵抗有关。