JCEM：过量食物刺激肝脏葡萄糖分泌

在肥胖人群，血浆甘油三脂（TG）浓度增加的确切机制仍不清楚，且能量摄入过量本身是否参与这种异常的病理生理仍不知道。为了验证一天中一次均衡膳食的能量摄入过量如何影响VLDL–TG的动力学，以及其可能的调节因子对肝脏胰岛素敏感性和血浆游离脂肪酸（FFA）的影响。来自美国华盛顿大学医学院的Bettina Mittendorfer教授及其团队进行了一项研究，该研究发现在超重/肥胖的男性，一天中度过量食物（能量摄入过量30%）刺激肝脏葡萄糖和VLDL-apoB-100的分泌率，但对肝脏和脂肪组织脂肪酸代谢没有影响。该研究结果在线发表在2013年6月7日的《临床内分泌代谢杂志》（The journal of clinical endocrinology & metabolism）上。

该研究中，在8例超重和肥胖的男性受试者（年龄：38±3岁；体重指数：33.7±1.7kg/m²；均数±标准误）中，两次使用稳定同位素标记示踪法评估葡萄糖和脂质动力学（随机交叉设计）：第一次，受试者进食一次均衡膳食后的第二日，给与与他们能量消耗相匹配的能量总量；下一次，受试者进食一次均衡膳食后的第二日，给予30%多余的热量。8例健康、消瘦的男性（34±1岁；体重指数：22.5±0.6kg/m²）同等热量条件下被研究，提供正常脂质动力学的参照。

该研究结果表明，超重/肥胖的男性与消瘦的男性相比，VLDL-TG和VLDL-apoB-100浓度和分泌率显著增加（P＜0.01）。在超重/肥胖的男性，高热量与等热量饮食相比，血浆葡萄糖显现率（904±21 vs 873±26umol/min）、肝脏胰岛素抵抗指数（10.9±2.2 vs 8.3±1.8）、以及VLDL-apoB-100浓度和分泌率（1.91±0.24 vs 1.53±0.13nmol/min）增加，然而，VLDL-apoB-100血浆清除率、VLDL-TG分泌和血浆清除率、以及血浆FFA显现率没有受到过量食物的影响。

该研究发现，在超重/肥胖的男性，一天中度过量食物（能量摄入过量30%）刺激肝脏葡萄糖和VLDL-apoB-100的分泌率，但对肝脏和脂肪组织脂肪酸代谢没有影响。

One day of mixed meal overfeeding reduces hepatic insulin sensitivity and increases VLDL particle but not VLDL-triglyceride secretion in overweight and obese men.
Abstract
Context:The exact mechanisms responsible for increased plasma triglyceride (TG) concentration in obese people are unclear and it is not known whether excess energy intake per se is involved in the pathophysiology of this abnormality.Objective:The purpose of our study was to examine how excess energy intake from a balanced diet for one day affects VLDL-TG kinetics and its putative regulators hepatic insulin sensitivity and plasma free fatty acid (FFA) availability.Subjects and Design:We used stable isotope labeled tracer methods to evaluate glucose and lipid kinetics in eight overweight and obese men (age: 38 ± 3 years; body mass index: 33.7 ± 1.7 kg/m2; means ± SEM) on two occasions (randomized cross-over design): once, the day after they consumed a balanced diet that provided an amount of energy that matched their energy expenditure and another time, the day after they consumed a balanced diet that provided 30% excess calories. Eight healthy, lean men (34 ± 1 years; 22.5 ± 0.6 kg/m2) were studied under isocaloric conditions only to provide a reference for "normal" lipid kinetics.Results:VLDL-TG and VLDL-apoB-100 concentrations and secretion rates were significantly greater (P< 0.01) in overweight/obese compared to lean men. Hypercaloric, compared with isocaloric feeding in overweight/obese men, increased glucose rate of appearance in plasma (904 ± 21 vs. 873 ± 26 μ mol·min-1), the hepatic insulin resistance index (10.9 ± 2.2 vs. 8.3 ± 1.8), and VLDL-apoB-100 concentration and secretion rate (1.91 ± 0.24 vs. 1.53 ± 0.13 nmol·min-1) whereas VLDL-apoB-100 plasma clearance rate, VLDL-TG secretion and plasma clearance rates, and FFA rate of appearance in plasma were not affected by overfeeding.Conclusion:One day of moderate overfeeding (30% excess energy intake) stimulates hepatic glucose and VLDL-apo-B-100 secretion rates but has no effect on hepatic and adipose tissue fatty acid metabolism in overweight/obese men.