Ketogenic diet attenuates hepatopathy in mouse model of respiratory chain complex III deficiency caused by a Bcs1l mutation

Research output: Contribution to journalArticle


Mitochondrial disorders are among the most prevalent inborn errors of metabolism but largely lack treatments and have poor outcomes. High-fat, low-carbohydrate ketogenic diets (KDs) have shown beneficial effects in mouse models of mitochondrial myopathies, with induction of mitochondrial biogenesis as the suggested main mechanism. We fed KD to mice with respiratory chain complex III (CIII) deficiency and progressive hepatopathy due to mutated BCS1L, a CIII assembly factor. The mutant mice became persistently ketotic and tolerated the KD for up to 11 weeks. Liver disease progression was attenuated by KD as shown by delayed fibrosis, reduced cell death, inhibition of hepatic progenitor cell response and stellate cell activation, and normalization of liver enzyme activities. Despite no clear signs of increased mitochondrial biogenesis in the liver, CIII assembly and activity were improved and mitochondrial morphology in hepatocytes normalized. Induction of hepatic glutathione transferase genes and elevated total glutathione level were normalized by KD. Histological findings and transcriptome changes indicated modulation of liver macrophage populations by the mutation and the diet. These results reveal a striking beneficial hepatic response to KD in mice with mitochondrial hepatopathy and warrant further investigations of dietary modification in the management of these conditions in patients.


  • Janne Purhonen
  • Jayasimman Rajendran
  • Matthias Mörgelin
  • Kristiina Uusi-Rauva
  • Shintaro Katayama
  • Kaarel Krjutskov
  • Elisabet Einarsdottir
  • Vidya Velagapudi
  • Juha Kere
  • Matti Jauhiainen
  • Vineta Fellman
  • Jukka Kallijärvi
External organisations
  • Folkhälsan Research Center
  • Karolinska Institutet
  • University of Helsinki
  • King's College London
  • Finnish National Institute for Health and Welfare
  • Helsinki University Central Hospital
  • Competence Centre on Health Technologies, Estonia
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Article number1109
JournalScientific Reports
Issue number1
Publication statusPublished - 2017 Apr 19
Publication categoryResearch