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

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Purhonen , J , Rajendran , J , Morgelin , M , Uusi-Rauva , K , Katayama , S , Krjutskov , K , Einarsdottir , E , Velagapudi , V , Kere , J , Jauhiainen , M , Fellman , V & Kallijarvi , J 2017 , ' Ketogenic diet attenuates hepatopathy in mouse model of respiratory chain complex III deficiency caused by a Bcs1l mutation ' , Scientific Reports , vol. 7 , 957 . https://doi.org/10.1038/s41598-017-01109-4

Title: Ketogenic diet attenuates hepatopathy in mouse model of respiratory chain complex III deficiency caused by a Bcs1l mutation
Author: Purhonen, Janne; Rajendran, Jayasimman; Morgelin, Matthias; Uusi-Rauva, Kristiina; Katayama, Shintaro; Krjutskov, Kaarel; Einarsdottir, Elisabet; Velagapudi, Vidya; Kere, Juha; Jauhiainen, Matti; Fellman, Vineta; Kallijarvi, Jukka
Contributor: University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Research Programs Unit
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, University of Helsinki
University of Helsinki, Children's Hospital
Date: 2017-04-19
Language: eng
Number of pages: 16
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/195631
Abstract: 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.
Subject: PROGENITOR-CELL EXPANSION
LOW-CARBOHYDRATE
GRACILE SYNDROME
GENE-EXPRESSION
IRON-OVERLOAD
MITOCHONDRIAL
LIVER
MACROPHAGES
MICE
DISEASE
3111 Biomedicine
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