An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans.
An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans.
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DOI：
10.1016/j.cmet.2018.01.005
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发表时间：
2018-03-06
期刊：
影响因子：
29
通讯作者：
Borén J
中科院分区：
文献类型：
--
作者：
Mardinoglu A;Wu H;Bjornson E;Zhang C;Hakkarainen A;Räsänen SM;Lee S;Mancina RM;Bergentall M;Pietiläinen KH;Söderlund S;Matikainen N;Ståhlman M;Bergh PO;Adiels M;Piening BD;Granér M;Lundbom N;Williams KJ;Romeo S;Nielsen J;Snyder M;Uhlén M;Bergström G;Perkins R;Marschall HU;Bäckhed F;Taskinen MR;Borén J
限制碳水化合物饮食是针对非酒精性脂肪性肝病（NAFLD）广泛推荐的一种干预措施，但缺乏对这种饮食多种益处的系统性视角。在此，我们对患有NAFLD的肥胖受试者进行了等热量低碳水化合物且蛋白质含量增加的短期干预，并使用多组学方法描述了代谢和肠道微生物群所产生的变化。我们观察到肝脏脂肪和其他心血管代谢风险因素迅速且显著降低，同时伴有：（1）肝脏从头脂肪生成显著减少；（2）血清β - 羟基丁酸浓度大幅增加，反映出线粒体β - 氧化增强；（3）产叶酸的链球菌和血清叶酸浓度快速增加。对第二个队列的活检样本进行的肝脏转录组分析显示，脂肪酸合成途径下调，叶酸介导的一碳代谢和脂肪酸氧化途径上调。我们的研究结果强调了探索饮食 - 微生物群相互作用用于治疗NAFLD的潜力。
马尔迪诺格鲁等人使用多组学研究限制碳水化合物饮食对肥胖NAFLD患者的影响。他们表明这种饮食改善了肝脏脂肪代谢，促进肠道微生物群的快速转变，增加循环叶酸，并上调肝脏中参与叶酸依赖的一碳代谢的基因表达。
A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum β-hydroxybutyrate concentrations, reflecting increased mitochondrial β-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD. Mardinoglu et al. use multi-omics to investigate the effects of a carbohydrate-restricted diet in obese NAFLD patients. They show that the diet improves liver fat metabolism, promotes rapid shifts in the gut microbiota, increases circulating folate, and upregulates expression of genes involved in folate-dependent one-carbon metabolism in the liver.
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影响因子：
13.5
作者：
Browning, Jeffrey D.;Davis, Jeannie;Burgess, Shawn C.
通讯作者：
Burgess, Shawn C.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
29
作者：
Badman, Michael K.;Pissios, Pavlos;Maratos-Flier, Eleftheria
通讯作者：
Maratos-Flier, Eleftheria
影响因子：
29
作者：
Chakravarthy, MV;Pan, ZJ;Semenkovich, CF
通讯作者：
Semenkovich, CF
影响因子：
5.8
作者：
Christodoulides, Constantinos;Dyson, Pamela;Karpe, Fredrik
通讯作者：
Karpe, Fredrik