Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease
Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease
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DOI：
10.1172/jci150996
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发表时间：
2021-12-15
影响因子：
15.9
通讯作者：
Vos, Miriam B.
中科院分区：
文献类型：
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作者：
Cohen, Catherine C.;Li, Kelvin W.;Vos, Miriam B.
背景资料。肝脏新生脂肪生成(DNL)在非酒精性脂肪性肝病(NAFLD)中升高。通过减少饮食中的糖来改善肝脏脂肪可能是通过降低DNL来调节的，但数据有限，尤其是在儿童中。我们研究了8周的饮食限制对患有NAFLD的青少年肝脏DNL的影响，以及DNL与其他代谢结果之间的相关性。方法：29名患有NAFLD的青少年男孩参加了一项为期8周的随机对照试验，比较低游离糖饮食和正常饮食。用重水7天代谢标记法测量肝脏DNL对血浆甘油三酯棕榈酸酯的贡献百分比。结果：治疗组肝脏DNL由34.6%降至24.1%，对照组由33.9%降至34.6%(调整后8周均值差：-10.6%[95%CI：-19.1%，-2.0%])，与此同时，肝脏脂肪(25.5%~17.9%比19.5%~18.8%)和空腹胰岛素(44.3~34.7比35.5~37.0mU/ml)的降幅更大。干预过程中糖耐量的变化与游离糖摄入量(r=0.48，P=0.011)、胰岛素(r=0.4，P=0.047)和丙氨酸氨基转移酶(ALT)(r=0.39，P=0.049)的变化显著相关，而与肝脂(r=0.13，P=0.532)无关。这些结果与肝脏DNL是连接膳食糖和NAFLD的关键代谢异常的假说是一致的。
BACKGROUND. Hepatic de novo lipogenesis (DNL) is elevated in nonalcoholic fatty liver disease (NAFLD). Improvements in hepatic fat by dietary sugar reduction may be mediated by reduced DNL, but data are limited, especially in children. We examined the effects of 8 weeks of dietary sugar restriction on hepatic DNL in adolescents with NAFLD and correlations between DNL and other metabolic outcomes.METHODS. Adolescent boys with NAFLD (n = 29) participated in an 8-week, randomized controlled trial comparing a diet low in free sugars versus their usual diet. Hepatic DNL was measured as percentage contribution to plasma triglyceride palmitate using a 7-day metabolic labeling protocol with heavy water. Hepatic fat was measured by magnetic resonance imaging-proton density fat fraction.RESULTS. Hepatic DNL was significantly decreased in the treatment group (from 34.6% to 24.1%) versus the control group (33.9% to 34.6%) (adjusted week 8 mean difference: -10.6% [95% CI: -19.1%, -2.0%]), which was paralleled by greater decreases in hepatic fat (25.5% to 17.9% vs. 19.5% to 18.8%) and fasting insulin (44.3 to 34.7 vs. 35.5 to 37.0 mu IU/mL). Percentage change in DNL during the intervention correlated significantly with changes in free-sugar intake (r = 0.48, P = 0.011), insulin (r = 0.40, P = 0.047), and alanine aminotransferase (ALT) (r = 0.39, P= 0.049), but not hepatic fat (r = 0.13, P= 0.532).CONCLUSION. Our results suggest that dietary sugar restriction reduces hepatic DNL and fasting insulin, in addition to reductions in hepatic fat and ALT, among adolescents with NAFLD. These results are consistent with the hypothesis that hepatic DNL is a critical metabolic abnormality linking dietary sugar and NAFLD.