Molecular Endocrinology and Genomics Center, Laval University Medical Research Center, Quebec City, Quebec, Canada G1V 4G2.
Metabolism. 2010 Aug;59(8):1106-14. doi: 10.1016/j.metabol.2009.09.034. Epub 2009 Dec 31.
Mutations in the lamin A/C gene (LMNA) cause lipodystrophy. However, little data are available on lamin A/C expression in various fat depots in women. We recruited 34 women scheduled for gynecologic surgery. Blood samples were collected on the morning of surgery to obtain a detailed lipid profile. Radiological examinations were performed to measure total body fat mass and abdominal fat accumulation. Fat samples were taken from the subcutaneous (SC) fat depot and from the greater omentum (OM) during the surgical procedure. Whole adipose tissue samples were used for total messenger RNA (mRNA) extraction and real-time polymerase chain reaction quantification of the LMNA transcript. No association was observed between lamin A/C mRNA expression, either in SC or OM fat tissue, and adiposity measures. Women with low SC lamin A/C expression, identified on the basis of the median value of SC lamin A/C mRNA expression, had a significantly altered lipid profile including lower levels of high-density lipoprotein (HDL) cholesterol and HDL(2) cholesterol and reduced HDL(2) cholesterol to HDL(3) cholesterol ratio (P < .05 for all). These women were also characterized by higher cholesterol to HDL cholesterol, low-density lipoprotein-triglycerides, very low-density lipoprotein-apolipoprotein B, and low-density lipoprotein cholesterol to HDL cholesterol (P < .05 for all). Low SC lamin A/C mRNA expression levels were also associated with significantly increased lipolysis in isolated fat cells from this fat depot. Specifically, the response to lipolytic agent isoproterenol was significantly increased at doses ranging from 10(-5) to 10(-10) mol/L (P < .05). A similar trend was observed in OM fat cells but did not reach significance. In conclusion, low lamin A/C expression in SC adipose tissue is associated with significant alterations in the lipid profile and increased fat cell lipolysis, independent of the level of total or abdominal adiposity.
lamin A/C 基因突变会导致脂肪营养不良。然而，关于女性不同脂肪组织中 lamin A/C 表达的数据很少。我们招募了 34 名计划接受妇科手术的女性。手术当天早上采集血样以获得详细的血脂谱。进行影像学检查以测量全身脂肪量和腹部脂肪堆积。在手术过程中从皮下（SC）脂肪组织和大网膜（OM）中取出脂肪样本。使用整个脂肪组织样本进行总信使 RNA（mRNA）提取和 lamin A/C 转录本的实时聚合酶链反应定量。在 SC 或 OM 脂肪组织中，lamin A/C mRNA 表达与肥胖指标之间没有关联。根据 SC lamin A/C mRNA 表达中位数确定的低 SC lamin A/C 表达的女性，其血脂谱明显改变，包括高密度脂蛋白（HDL）胆固醇和 HDL（2）胆固醇水平较低，以及 HDL（2）胆固醇与 HDL（3）胆固醇比值降低（所有 P 值均 <.05）。这些女性还具有胆固醇与 HDL 胆固醇、低密度脂蛋白-甘油三酯、极低密度脂蛋白-载脂蛋白 B 和低密度脂蛋白胆固醇与 HDL 胆固醇比值升高的特征（所有 P 值均 <.05）。低 SC lamin A/C mRNA 表达水平也与该脂肪组织中分离的脂肪细胞的脂肪分解明显增加相关。具体而言，在 10（-5）至 10（-10）mol/L 的剂量范围内，对脂肪分解剂异丙肾上腺素的反应明显增加（P <.05）。在 OM 脂肪细胞中观察到类似的趋势，但未达到显著水平。总之，SC 脂肪组织中 lamin A/C 表达降低与血脂谱的显著改变以及脂肪细胞脂肪分解增加有关，而与总脂肪量或腹部肥胖无关。
