Autor: |
Petersen, Kitt Falk, Dufour, Sylvie, Mehal, Wajahat Z., Shulman, Gerald I. |
Zdroj: |
Cell Metabolism; Nov2024, Vol. 36 Issue 11, p2359-23236, 20878p |
Abstrakt: |
We assessed in vivo rates of hepatic mitochondrial oxidation, gluconeogenesis, and β-hydroxybutyrate (β-OHB) turnover by positional isotopomer NMR tracer analysis (PINTA) in individuals with metabolic-dysfunction-associated steatotic liver (MASL) (fatty liver) and MASL disease (MASLD) (steatohepatitis) compared with BMI-matched control participants with no 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 groups compared with the control group. A physiological increase in plasma glucagon concentrations increased in vivo rates of hepatic mitochondrial oxidation by 50%–75% in individuals with and without MASL and increased rates of glucose production by ∼50% in the MASL group, which could be attributed in part to an ∼30% increase in rates of mitochondrial pyruvate carboxylase flux. These results demonstrate that (1) rates of hepatic mitochondrial oxidation are not substantially altered in individuals with MASL and MASLD and (2) glucagon increases rates of hepatic mitochondrial oxidation. [Display omitted] • Hepatic mitochondrial oxidation is not altered in humans with fatty liver • Hepatic mitochondrial oxidation is not altered in humans with steatohepatitis • Glucagon increases hepatic mitochondrial oxidation in humans without fatty liver • Glucagon increases hepatic mitochondrial oxidation in humans with fatty liver It is unclear whether rates of hepatic mitochondrial oxidation are altered in individuals with MASLD and MASH. Here, Petersen et al. show that rates of hepatic mitochondrial oxidation are not altered in humans with fatty liver or steatohepatitis and that glucagon can increase rates of hepatic mitochondrial oxidation in humans with and without fatty liver by 50%–75%. [ABSTRACT FROM AUTHOR] |
Databáze: |
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