Liver knockout of MCU leads to greater dysregulation of lipid metabolism in MAFLD

Sci Rep. 2024 Nov 15;14(1):28167. doi: 10.1038/s41598-024-78935-w.

Abstract

Metabolic-associated fatty liver disease (MAFLD) is a common chronic condition that poses a significant threat to human health. Mitochondrial dysfunction, particularly involving the mitochondrial Ca2+ uniporter (MCU), plays a key role in its pathogenesis. This study aimed to investigate the impact of the MCU gene on hepatic lipid metabolism in mice fed a high-fat diet. Using MCU knockout and wild-type mice, subjected to either a high-fat or normal diet for 14 weeks, we observed notable Steatosis and liver weight gain in MCU-deficient mice. Liver function markers, serum triglycerides, very low-density lipoprotein (VLDL) levels, and ApoB protein expression were all significantly elevated. Mechanistic studies revealed that MCU deletion led to mitochondrial dysfunction, increased oxidative stress. These findings highlight the critical role of the MCU gene in maintaining hepatic lipid balance and suggest its potential as a therapeutic target for managing nonalcoholic fatty liver disease.

Keywords: Fat liver; Lipid dysregulation; Lipid transport-associated; MAFLD; MCU.

MeSH terms

  • Animals
  • Calcium Channels* / genetics
  • Calcium Channels* / metabolism
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Lipid Metabolism* / genetics
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • Non-alcoholic Fatty Liver Disease* / genetics
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Oxidative Stress
  • Triglycerides / blood
  • Triglycerides / metabolism

Substances

  • Calcium Channels
  • mitochondrial calcium uniporter
  • Triglycerides