Mingrone Geltrude, Manco Melania, Granato Luigi, Calvani Menotti, Scarfone Antonio, Mora Elena Valera, Greco Aldo V, Vidal Hubert, Castagneto Marco, Ferrannini Eleuterio
Department of Internal Medicine, CNR Centro di Fisiopatologia dello Shock, Catholic University, School of Medicine, Rome, Italy.
FASEB J. 2005 Aug;19(10):1380-2. doi: 10.1096/fj.04-3453fje. Epub 2005 Jun 13.
Plasma leptin and growth hormone (GH) profile and pulsatility have been studied in morbidly obese subjects before and 14 months after bilio-pancreatic diversion (BPD), a bariatric technique producing massive lipid malabsorption. The maximum leptin diurnal variation (acrophase) decreased (10.27+/-1.70 vs. 22.60+/-2.79 ng x ml(-1); P=0.001), while its pulsatility index (PI) increased (1.084+/-0.005 vs. 1.050+/-0.004 ng x ml(-1) x min(-1); P=0.02) after BPD. Plasma GH acrophase increased (P=0.0001) from 0.91+/-0.20 to 4.58+/-0.80 microg x l(-1) x min(-1) after BPD as well as GH PI (1.70+/-0.13 vs. 1.20+/-0.04 microg x l(-1) x min(-1); P=0.024). Whole-body glucose uptake (M), assessed by euglycemic-hyperinsulinemic clamp, almost doubled after BPD (from 0.274+/-0.022 to 0.573+/-0.027 mmol x kgFFM(-1) x min(-1); P<0.0001), while 24 h lipid oxidation was significantly (P<0.0001) reduced (131.94+/-35.58 vs. 44.56+/-15.10 g). However, the average lipid oxidation was 97.2+/-3.1% (P<0.01) of the metabolizable lipid intake after the bariatric operation, while it was 69.2+/-8.5% before. After the operation, skeletal muscle ACC2 mRNA decreased (P<0.0001) from 452.82+/-76.35 to 182.45+/-40.69% of cyclophilin mRNA as did the malonyl-CoA (from 0.28+/-0.02 to 0.16+/-0.01 nmol x g(-1); P<0.0001). Leptin changes negatively correlated with M changes (R2=0.69, P<0.001). In a stepwise regression (R2=0.87, P=0.0055), only changes in 24 h free fatty acids (B=0.105+/-0.018, P=0.002) and glucose/insulin ratio (B=0.247+/-0.081, P=0.029) were the best predictors of leptin variations. In conclusion, the reversion of insulin resistance after BPD might allow reversal of leptin resistance, restoration of leptin pulsatility, and consequent inhibition of ACC2 mRNA expression, translating to a reduced synthesis of malonyl-CoA, which, in turn, results in increased fatty acid oxidation. Finally, since leptin inhibits GH secretion, a reduction of circulating leptin levels might have produced an increase in GH secretion, as observed in our series.
在胆胰转流术（BPD）（一种导致大量脂质吸收不良的减肥手术）前后，对病态肥胖受试者的血浆瘦素和生长激素（GH）水平及脉冲性进行了研究。BPD术后，瘦素的最大昼夜变化（峰值相位）降低（10.27±1.70对22.60±2.79 ng·ml⁻¹；P = 0.001），而其脉冲指数（PI）增加（1.084±0.005对1.050±0.004 ng·ml⁻¹·min⁻¹；P = 0.02）。BPD术后血浆GH峰值相位从0.91±0.20增加到4.58±0.80 μg·l⁻¹·min⁻¹（P = 0.0001），GH的PI也增加（1.70±0.13对1.20±0.04 μg·l⁻¹·min⁻¹；P = 0.024）。通过正常血糖高胰岛素钳夹评估的全身葡萄糖摄取（M）在BPD术后几乎翻倍（从0.274±0.022增加到0.573±0.027 mmol·kg去脂体重⁻¹·min⁻¹；P < 0.0001），而24小时脂质氧化显著降低（P < 0.0001）（131.94±35.58对44.56±15.10 g）。然而，减肥手术后平均脂质氧化占可代谢脂质摄入量的97.2±3.1%（P < 0.01），而术前为69.2±8.5%。术后，骨骼肌ACC2 mRNA从亲环素mRNA的452.82±76.35%降至182.45±40.69%（P < 0.0001），丙二酰辅酶A也下降（从0.28±0.02降至0.16±0.01 nmol·g⁻¹；P < 0.0001）。瘦素变化与M变化呈负相关（R² = 0.69，P < 0.001）。在逐步回归分析中（R² = 0.87，P = 0.0055），只有24小时游离脂肪酸变化（B = 0.105±0.018，P = 0.002）和葡萄糖/胰岛素比值变化（B = 0.247±0.081，P = 0.029）是瘦素变化的最佳预测指标。总之，BPD术后胰岛素抵抗的逆转可能使瘦素抵抗逆转，瘦素脉冲性恢复，并进而抑制ACC2 mRNA表达，导致丙二酰辅酶A合成减少，这反过来又导致脂肪酸氧化增加。最后，由于瘦素抑制GH分泌，如我们的研究系列中所观察到的，循环瘦素水平的降低可能导致GH分泌增加。
