Endocrinology and Diabetes Unit, Joan XXIII University Hospital, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
PLoS One. 2013 May 20;8(5):e63937. doi: 10.1371/journal.pone.0063937. Print 2013.
Munc18c is associated with glucose metabolism and could play a relevant role in obesity. However, little is known about the regulation of Munc18c expression. We analyzed Munc18c gene expression in human visceral (VAT) and subcutaneous (SAT) adipose tissue and its relationship with obesity and insulin.
We evaluated 70 subjects distributed in 12 non-obese lean subjects, 23 overweight subjects, 12 obese subjects and 23 nondiabetic morbidly obese patients (11 with low insulin resistance and 12 with high insulin resistance).
The lean, overweight and obese persons had a greater Munc18c gene expression in adipose tissue than the morbidly obese patients (p<0.001). VAT Munc18c gene expression was predicted by the body mass index (B = -0.001, p = 0.009). In SAT, no associations were found by different multiple regression analysis models. SAT Munc18c gene expression was the main determinant of the improvement in the HOMA-IR index 15 days after bariatric surgery (B = -2148.4, p = 0.038). SAT explant cultures showed that insulin produced a significant down-regulation of Munc18c gene expression (p = 0.048). This decrease was also obtained when explants were incubated with liver X receptor alpha (LXRα) agonist, either without (p = 0.038) or with insulin (p = 0.050). However, Munc18c gene expression was not affected when explants were incubated with insulin plus a sterol regulatory element-binding protein-1c (SREBP-1c) inhibitor (p = 0.504).
Munc18c gene expression in human adipose tissue is down-regulated in morbid obesity. Insulin may have an effect on the Munc18c expression, probably through LXRα and SREBP-1c.
Munc18c 与葡萄糖代谢有关，在肥胖中可能发挥重要作用。然而，关于 Munc18c 表达的调控知之甚少。我们分析了人内脏（VAT）和皮下（SAT）脂肪组织中 Munc18c 基因的表达及其与肥胖和胰岛素的关系。
我们评估了 70 名受试者，分为 12 名非肥胖的瘦受试者、23 名超重受试者、12 名肥胖受试者和 23 名非糖尿病的病态肥胖患者（11 名胰岛素抵抗低和 12 名胰岛素抵抗高）。
瘦、超重和肥胖者的脂肪组织中 Munc18c 基因表达高于病态肥胖患者（p<0.001）。VAT Munc18c 基因表达可由体重指数（B = -0.001，p = 0.009）预测。在 SAT 中，不同的多元回归分析模型均未发现相关性。SAT Munc18c 基因表达是减肥手术后 15 天 HOMA-IR 指数改善的主要决定因素（B = -2148.4，p = 0.038）。SAT 组织培养显示，胰岛素显著下调 Munc18c 基因表达（p = 0.048）。在没有（p = 0.038）或有胰岛素（p = 0.050）的情况下，用肝 X 受体α（LXRα）激动剂孵育外植体时也会发生这种减少。然而，当外植体与胰岛素加固醇调节元件结合蛋白-1c（SREBP-1c）抑制剂孵育时，Munc18c 基因表达不受影响（p = 0.504）。
人脂肪组织中 Munc18c 基因的表达在病态肥胖中下调。胰岛素可能对 Munc18c 的表达有影响，可能通过 LXRα 和 SREBP-1c。
