Mingrone Geltrude, Manco Melania, Iaconelli Amerigo, Gniuli Donatella, Bracaglia Roberto, Leccesi Laura, Calvani Menotti, Nolfe Giuseppe, Basu Subhabrata, Berria Rachele
Department of Internal Medicine, Università Cattolica S. Cuore, Rome, Italy.
Obesity (Silver Spring). 2008 Aug;16(8):1831-7. doi: 10.1038/oby.2008.297. Epub 2008 Jun 5.
Hyperprolactinemia is associated with obesity. Furthermore, in human adipose tissue cultured in vitro, prolactin (PRL) inhibited lipoprotein lipase (LPL) activity via functional PRL receptors.
To study PRL and insulin ultradian rhythm and subcutaneous adipose tissue LPL mRNA and protein expressions in severely obese women before and after malabsorptive bariatric surgery.
Seven severely obese, fertile women were studied twice, once before and the second time 1 year after bilio-pancreatic diversion (BPD), when the weight was stable for at least 3 months. Metabolizable energy intake and 24-h energy expenditure (EE) were measured. Fourier and PULSEFIT analyses were applied to 24-h hormonal time-series to study daily fluctuations and hormonal clearance. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp. Quantitative-competitive reverse transcriptase-PCR and western blot analysis were used to measure LPL gene expression.
Spontaneous 24-h PRL secretion was significantly reduced after BPD (mean-daily release, 128.4 +/- 28.1 microg/l vs. 67.2 +/- 9.2 microg/l distribution volume (Vd/l.24 h), P = 0.02); insulin secretion also was significantly reduced (499.9 +/- 204.0 microg/Vd/l.24 h vs. 85.6 +/- 21.0 microg/Vd/l.24 h, P = 0.0001). Metabolizable energy/kg(FFM) did not change significantly after BPD. Twenty-four-hour EE, but not 24-h EE/FFM, was significantly decreased after BPD (P < 0.05). Insulin sensitivity significantly (P < 0.0001) increased after BPD from 21.41 +/- 1.92 to 68.62 +/- 5.03 micromol/kg(FFM)/min. LPL mRNA concentration (from 42.63 +/- 4.21% to 19.00 +/- 2.74% of cyclophilin mRNA, P = 0.001) as well as LPL protein level (from 8.94 +/- 2.73 to 3.16 +/- 1.05 as ratios of protein of interest vs. housekeeping protein, P = 0.038) significantly decreased after BPD. The major determinant of PRL secretion was insulin secretion, whereas the best predictors of LPL expression were insulin and PRL secretion rates.
The restriction of lipid metabolizable energy rather than weight loss seems to be responsible for both reduction in PRL circulating levels and normalization of its secretion rhythm after bariatric surgery. Furthermore, the reduced adipose tissue LPL expression, being significantly correlated with the decrease in insulin and PRL, suggests a role of hyperinsulinemia and hyperprolactinemia in inducing and sustaining obesity.
高催乳素血症与肥胖相关。此外，在体外培养的人体脂肪组织中，催乳素（PRL）通过功能性PRL受体抑制脂蛋白脂肪酶（LPL）活性。
研究严重肥胖女性在进行吸收不良性减肥手术后，PRL和胰岛素的超日节律以及皮下脂肪组织LPL mRNA和蛋白表达情况。
对7名严重肥胖的育龄女性进行了两次研究，一次是在胆胰转流术（BPD）前，第二次是在术后1年，此时体重已稳定至少3个月。测量了可代谢能量摄入和24小时能量消耗（EE）。对24小时激素时间序列应用傅里叶分析和PULSEFIT分析，以研究每日波动和激素清除情况。通过正常血糖-高胰岛素钳夹技术评估胰岛素敏感性。采用定量竞争性逆转录-聚合酶链反应和蛋白质印迹分析来测量LPL基因表达。
BPD术后自发性24小时PRL分泌显著降低（平均每日释放量，128.4±28.1μg/l对67.2±9.2μg/l分布容积（Vd/l.24 h），P = 0.02）；胰岛素分泌也显著降低（499.9±204.0μg/Vd/l.2 的24小时，P = 0.0001）。BPD术后可代谢能量/千克（去脂体重）无显著变化。BPD术后24小时EE显著降低（P < 0.05），但24小时EE/去脂体重未降低。BPD术后胰岛素敏感性显著增加（P < 0.0001），从21.41±1.92增加到68.62±5.03μmol/千克（去脂体重）/分钟。BPD术后LPL mRNA浓度（从亲环蛋白mRNA的42.63±4.21%降至19.00±2.74%，P = 0.001）以及LPL蛋白水平（从目的蛋白与管家蛋白的比值8.94±2.73降至3.16±1.05，P = 0.038）均显著降低。PRL分泌的主要决定因素是胰岛素分泌，而LPL表达的最佳预测指标是胰岛素和PRL分泌率。
减肥手术后，PRL循环水平降低及其分泌节律正常化似乎是由于脂质可代谢能量的限制而非体重减轻。此外，脂肪组织LPL表达降低与胰岛素和PRL的降低显著相关，提示高胰岛素血症和高催乳素血症在诱导和维持肥胖中起作用。
