美国耶鲁大学Gerald I. Shulman等研究人员合作发现，胰高血糖素促进脂肪肝患者肝脏线粒体氧化和丙酮酸羧化酶通量的增加。这一研究成果于2024年8月27日在线发表在国际学术期刊《细胞—代谢》上。

研究人员通过位置同位素核磁共振示踪分析（PINTA）评估了代谢功能障碍相关脂肪肝（MASL）和MASL疾病（MASLD）（脂肪性肝炎）患者的肝脏线粒体氧化、糖异生和β-羟基丁酸（β-OHB）周转的体内速率，并与无肝脂肪变性的BMI匹配的对照参与者进行了比较。肝脂肪含量被局部¹H磁共振波谱（MRS）所量化。

研究人员发现，与对照组相比，MASL和MASLD组的肝脏线粒体氧化速率在体内没有显著改变。生理性升高的血浆胰高血糖素浓度，使得MASL和非MASL患者的肝脏线粒体氧化速率在体内增加了50%至75%，并使得MASL组的葡萄糖生成速率增加了约50%，这部分归因于线粒体丙酮酸羧化酶通量速率增加了约30%。

这些结果表明：(1) MASL和MASLD患者的肝脏线粒体氧化速率没有显著改变；(2) 胰高血糖素可以增加肝脏线粒体氧化速率。

附：英文原文

Title: Glucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease

Author: Kitt Falk Petersen, Sylvie Dufour, Wajahat Z. Mehal, Gerald I. Shulman

Issue&Volume: 2024-08-27

Abstract: We assessed in vivo rates of hepatic mitochondrial oxidation, gluconeogenesis, and β-hydroxybutyrate(β-OHB) turnover by positional isotopomer NMR tracer analysis (PINTA) in individualswith metabolic-dysfunction-associated steatotic liver (MASL) (fatty liver) and MASLdisease (MASLD) (steatohepatitis) compared with BMI-matched control participants withno hepatic steatosis. Hepatic fat content was quantified by localized 1H magnetic resonance spectroscopy (MRS). We found that in vivo rates of hepatic mitochondrial oxidation were unaltered in the MASL and MASLD groupscompared with the control group. A physiological increase in plasma glucagon concentrationsincreased in vivo rates of hepatic mitochondrial oxidation by 50%–75% in individuals with and withoutMASL and increased rates of glucose production by ～50% in the MASL group, which couldbe attributed in part to an ～30% increase in rates of mitochondrial pyruvate carboxylaseflux. These results demonstrate that (1) rates of hepatic mitochondrial oxidationare not substantially altered in individuals with MASL and MASLD and (2) glucagonincreases rates of hepatic mitochondrial oxidation.

DOI: 10.1016/j.cmet.2024.07.023

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00325-5