生酮饮食改善NAFLD的机制
创作:szx 审核:szx 2020年03月22日
  • 纳入10名NAFLD患者,进行为期6天的生酮饮食干预;
  • 生酮饮食降低了31%的肝脏内甘油三酯(IHTG),并降低了3%的体重及58%的肝脏胰岛素抵抗,但增加了35%的非酯化脂肪酸(NEFA,可作为IHTG的合成底物);
  • 上述作用可归因于生酮饮食引起的血清胰岛素及肝脏柠檬酸合酶通量的降低,以增加IHTG的净水解并促进脂肪酸的生酮作用;
  • 生酮饮食可增加肝脏线粒体氧化还原状态,并降低血浆中的瘦素及三碘甲状腺氨酸的浓度。
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szx
生酮饮食可快速逆转非酒精性脂肪性肝病(NAFLD)及胰岛素抵抗。来自PNAS上发表的一项最新研究,揭示了生酮饮食改善NAFLD的机制:生酮饮食可通过改变肝脏线粒体的氧化还原状态,促进肝脏内甘油三酯的水解并增加脂肪酸的生酮作用,从而降低肝脏脂肪含量及胰岛素抵抗。
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PNAS [IF:9.412]

Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease

生酮饮食对非酒精性脂肪性肝病患者的肝性脂肪变性及肝脏线粒体代谢的影响

10.1073/pnas.1922344117

2020-03-16, Article

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Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope infusions of: [D7]glucose, [13C4]β-hydroxybutyrate and [3-13C]lactate before and after a 6-d KD. IHTG was determined by proton magnetic resonance spectroscopy (1H-MRS). The KD diet decreased IHTG by 31% in the face of a 3% decrease in body weight and decreased hepatic insulin resistance (−58%) despite an increase in NEFA concentrations (+35%). These changes were attributed to increased net hydrolysis of IHTG and partitioning of the resulting fatty acids toward ketogenesis (+232%) due to reductions in serum insulin concentrations (−53%) and hepatic citrate synthase flux (−38%), respectively. The former was attributed to decreased hepatic insulin resistance and the latter to increased hepatic mitochondrial redox state (+167%) and decreased plasma leptin (−45%) and triiodothyronine (−21%) concentrations. These data demonstrate heretofore undescribed adaptations underlying the reversal of NAFLD by KD: That is, markedly altered hepatic mitochondrial fluxes and redox state to promote ketogenesis rather than synthesis of IHTG.

First Authors:
Panu K Luukkonen

Correspondence Authors:
Gerald I Shulman,Hannele Yki-Järvinen

All Authors:
Panu K Luukkonen,Sylvie Dufour,Kun Lyu,Xian-Man Zhang,Antti Hakkarainen,Tiina E Lehtimäki,Gary W Cline,Kitt Falk Petersen,Gerald I Shulman,Hannele Yki-Järvinen

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