Mingrone G, Rosa G, Greco A V, Manco M, Vega N, Nanni G, Castagneto M, Vidal H
Istituto di Clinica Medica, Università Cattolica del Sacro Cuore, Rome, Italy.
Atherosclerosis. 2003 Sep;170(1):155-61. doi: 10.1016/s0021-9150(03)00254-5.
The aim of this study was to investigate the sterol regulatory element-binding protein 1c (SREBP1c) mRNA muscle expression in morbid obese subjects before and after massive lipid malabsorption due to bariatric surgery (bilio-pancreatic diversion, BPD). We studied 11 obese subjects (BMI 49+/-2 kg/m2) before and 24 months after BPD. Skeletal muscle SREBP1c mRNA expression was determined using RT-competitive PCR. Intramyocytic triglycerides were quantified by HPLC. Insulin sensitivity (M/I) was assessed by euglycemic-hyperinsulinemic clamp. Energy expenditure and respiratory quotient (RQ) were measured over 24 h in a calorimetric chamber. Total cardiovascular risk dropped from 2 before to -2.5 after BPD (P<0.0001). The M/I value was normalized after surgery (0.036+/-0.0148 to 0.095+/-0.0147 micromol kgFFM(-1) min(-1) pmoles(-1) P<0.001). SREBP-1c mRNA levels were decreased (from 4.12+/-2.43 to 2.69+/-1.83% of cyclophilin mRNA, P=0.02) after BPD. In a multiple regression analysis, M/I values (P<0.0001) as well as the intramyocytic triglyceride levels (P=0.039) were the most powerful independent variables for predicting cardiovascular risk. Our results show that the reduction of cardiovascular risk after bariatric massive weight loss is strongly related to the reversion of insulin resistance and to the lowering of intramyocytic triglyceride depots. These two parameters are associated with a significant reduction in SREBP-1c mRNA expression in skeletal muscle, suggesting that this transcription factor might be involved in the accumulation of triglycerides in muscle cells of morbidly obese subjects.
本研究旨在调查病态肥胖受试者在接受减肥手术（胆胰转流术，BPD）导致大量脂质吸收不良前后，固醇调节元件结合蛋白1c（SREBP1c）mRNA在肌肉中的表达情况。我们对11名肥胖受试者（BMI 49±2 kg/m²）在BPD术前及术后24个月进行了研究。采用RT竞争PCR法测定骨骼肌SREBP1c mRNA表达。通过HPLC对肌细胞内甘油三酯进行定量分析。采用正常血糖高胰岛素钳夹技术评估胰岛素敏感性（M/I）。在热量测定室中测量24小时的能量消耗和呼吸商（RQ）。BPD术后总的心血管风险从术前的2降至术后的-2.5（P<0.0001）。术后M/I值恢复正常（从0.036±0.0148至0.095±0.0147 μmol kgFFM⁻¹ min⁻¹ pmoles⁻¹，P<0.001）。BPD术后SREBP-1c mRNA水平降低（从亲环素mRNA的4.12±2.43%降至2.69±1.83%，P = 0.02）。在多元回归分析中，M/I值（P<0.0001）以及肌细胞内甘油三酯水平（P = 0.039）是预测心血管风险最有力的独立变量。我们的研究结果表明，减肥手术后心血管风险的降低与胰岛素抵抗的逆转以及肌细胞内甘油三酯储存的减少密切相关。这两个参数与骨骼肌中SREBP-1c mRNA表达的显著降低相关，提示该转录因子可能参与了病态肥胖受试者肌肉细胞中甘油三酯的积累。
