Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans

Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans
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DOI:
10.3945/ajcn.112.038695
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发表时间:
2012-10-01
影响因子:
7.1
通讯作者:
Yki-Jarvinen, Hannele
Yki-Jarvinen, Hannele
中科院分区:
医学1区
文献类型:
--
作者:
Sevastianova, Ksenia;Santos, Alexandre;Yki-Jarvinen, Hannele

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背景资料:横断面研究已经确定大量摄入单糖是预测非酒精性脂肪性肝病(NAFLD)的一个重要饮食因素。目的:我们研究了过量摄入单糖是否会增加超重受试者的肝脏脂肪和新生脂肪生成(DNL),以及这是否可以通过减肥逆转。设计:16名受试者[BMI(kg/m2):30.6 +/- 1.2]进行高热量饮食(>1000 kcal简单碳水化合物/d)3周,然后进行低热量饮食6个月。对受试者进行PNPLA 3基因中rs739409的基因分型。在过度喂养之前和之后以及低热量饮食之后,测量代谢变量和肝脏脂肪(通过质子磁共振光谱测量)。结果:碳水化合物过量喂养使体重(+/- SEM)增加2%(1.8 +/- 0.3 kg; P < 0.0001),肝脏脂肪增加27%(从9.2 +/- 1.9%增加到11.7 +/- 1.9%(P = 0.005))。在PNPLA 3 - 148 II受试者中,DNL的增加与肝脏脂肪和血清甘油三酯的增加成比例,但在PNPLA 3 - 148 MM受试者中则不然。在低热量饮食期间,受试者体重减轻了4%(3.2 +/- 0.6 kg; P < 0.0001)和25%的肝脏脂肪含量(从11.7 +/- 1.9%到8.8 +/- 1.8%; P < 0.05)。碳水化合物过量喂养3周导致肝脏脂肪(27%)的相对变化比体重(2%)大10倍以上。肝脂肪的增加与DNL的增加成正比。减肥使肝脏脂肪恢复正常。这些数据表明,人类脂肪肝在碳水化合物过度喂养期间贪婪地积累脂肪,并支持DNL在NAFLD发病机制中的作用。该试验在www.hus.fi上注册为235780。美国临床营养杂志2012;96:727-34。
Background: Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease (NAFLD).Objective: We examined whether overfeeding overweight subjects with simple sugars increases liver fat and de novo lipogenesis (DNL) and whether this is reversible by weight loss.Design: Sixteen subjects [BMI (kg/m(2)): 30.6 +/- 1.2] were placed on a hypercaloric diet (>1000 kcal simple carbohydrates/d) for 3 wk and, thereafter, on a hypocaloric diet for 6 mo. The subjects were genotyped for rs739409 in the PNPLA3 gene. Before and after overfeeding and after hypocaloric diet, metabolic variables and liver fat (measured by proton magnetic resonance spectroscopy) were measured. The ratio of palmitate (16:0) to linoleate (18:2n-6) in serum and VLDL triglycerides was used as an index of DNL.Results: Carbohydrate overfeeding increased weight (+/- SEM) by 2% (1.8 +/- 0.3 kg; P < 0.0001) and liver fat by 27% from 9.2 +/- 1.9% to 11.7 +/- 1.9% (P = 0.005). DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3-148II but not PNPLA3-148MM. During the hypocaloric diet, the subjects lost 4% of their weight (3.2 +/- 0.6 kg; P < 0.0001) and 25% of their liver fat content (from 11.7 +/- 1.9% to 8.8 +/- 1.8%; P < 0.05).Conclusions: Carbohydrate overfeeding for 3 wk induced a >10-fold greater relative change in liver fat (27%) than in body weight (2%). The increase in liver fat was proportional to that in DNL. Weight loss restores liver fat to normal. These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD. This trial was registered at www.hus.fi as 235780. Am J Clin Nutr 2012;96:727-34.