Xu Chenchen, Markova Mariya, Seebeck Nicole, Loft Anne, Hornemann Silke, Gantert Thomas, Kabisch Stefan, Herz Kathleen, Loske Jennifer, Ost Mario, Coleman Verena, Klauschen Frederick, Rosenthal Anke, Lange Volker, Machann Jürgen, Klaus Susanne, Grune Tilman, Herzig Stephan, Pivovarova-Ramich Olga, Pfeiffer Andreas F H
Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany.
German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.
Liver Int. 2020 Dec;40(12):2982-2997. doi: 10.1111/liv.14596. Epub 2020 Jul 21.
Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low- (LP) or high-protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved.
19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500-1600 kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery.
IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3 weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA-seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of β-oxidation genes did not increase in the HP group.
HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.
非酒精性脂肪性肝病（NAFLD）日益普遍，营养干预仍是NAFLD最重要的治疗方法。我们的目的是研究低蛋白（LP）或高蛋白（HP）饮食在减少肝脏脂肪和逆转NAFLD方面是否更有效，以及涉及哪些机制。
19名接受减肥手术的病态肥胖参与者在手术前3周被随机分为两个低热量（1500 - 1600千卡/天）饮食组，一个低蛋白组（蛋白质占10E%）和一个高蛋白组（蛋白质占30E%）。在饮食干预前后测量肝内脂质水平（IHL）和血清成纤维细胞生长因子21（FGF21）。对手术期间采集的肝脏样本进行自噬通量、组织学、线粒体活性和基因表达分析。
HP组的IHL水平下降了42.6%，而LP组尽管体重减轻相似，但IHL水平没有显著变化。仅在LP组中，3周后肝脏自噬通量和血清FGF21分别增加了66.7%和42.2%。与LP组相比，HP组中脂肪摄取和脂质生物合成基因的表达水平较低。RNA测序分析显示，HP饮食后炎症途径的活性较低。HP组的肝脏线粒体活性和β氧化基因的表达没有增加。
尽管自噬和FGF21水平较低，但HP饮食比LP饮食更有效地减少肝脏脂肪。我们的数据表明，HP饮食导致肝脏脂肪减少主要是由于脂肪摄取和脂质生物合成受到抑制。
