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

Show simple item record 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 2017-06-29T06:39:04Z 2017-06-29T06:39:04Z 2017-04-19
dc.identifier.citation 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 .
dc.identifier.other PURE: 86199442
dc.identifier.other PURE UUID: 5c5c6461-2750-494c-a15b-566f8497a0d5
dc.identifier.other WOS: 000399536300013
dc.identifier.other Scopus: 85018392865
dc.description.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. en
dc.format.extent 16
dc.language.iso eng
dc.relation.ispartof Scientific Reports
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject IRON-OVERLOAD
dc.subject LIVER
dc.subject MACROPHAGES
dc.subject MICE
dc.subject DISEASE
dc.subject 3111 Biomedicine
dc.title Ketogenic diet attenuates hepatopathy in mouse model of respiratory chain complex III deficiency caused by a Bcs1l mutation en
dc.type Article
dc.contributor.organization Research Programme for Molecular Neurology
dc.contributor.organization University of Helsinki
dc.contributor.organization Research Programs Unit
dc.contributor.organization Päivi Marjaana Saavalainen / Principal Investigator
dc.contributor.organization Research Programme of Molecular Medicine
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Juha Kere / Principal Investigator
dc.contributor.organization Children's Hospital
dc.contributor.organization Lastentautien yksikkö
dc.contributor.organization Clinicum
dc.contributor.organization HUS Children and Adolescents
dc.description.reviewstatus Peer reviewed
dc.relation.issn 2045-2322
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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