Stankova 2020 Int J Mol Sci

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Staňková P, Kučera O, Peterová E, Lotková H, Maseko TE, Nožičková K, Červinková Z (2020) Adaptation of mitochondrial substrate flux in a mouse model of nonalcoholic fatty liver disease. Int J Mol Sci 21:E1101.

» PMID: 32046101 Open Access

Stankova Pavla, Kucera Otto, Peterova Eva, Lotkova Halka, Maseko Tumisang Edward, Nozickova Katerina, Cervinkova Zuzana (2020) Int J Mol Sci

Abstract: Maladaptation of mitochondrial oxidative flux seems to be a considerable feature of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to induce NAFLD in mice fed a Western-style diet (WD) and to evaluate liver mitochondrial functions. Experiments were performed on male C57BL/6J mice fed with a control diet or a WD for 24 weeks. Histological changes in liver and adipose tissue as well as hepatic expression of fibrotic and inflammatory genes and proteins were evaluated. The mitochondrial respiration was assessed by high-resolution respirometry. Oxidative stress was evaluated by measuring lipoperoxidation, glutathione, and reactive oxygen species level. Feeding mice a WD induced adipose tissue inflammation and massive liver steatosis accompanied by mild inflammation and fibrosis. We found decreased succinate-activated mitochondrial respiration and decreased succinate dehydrogenase (SDH) activity in the mice fed a WD. The oxidative flux with other substrates was not affected. We observed increased ketogenic capacity, but no impact on the capacity for fatty acid oxidation. We did not confirm the presence of oxidative stress. Mitochondria in this stage of the disease are adapted to increased substrate flux. However, inhibition of SDH can lead to the accumulation of succinate, an important signaling molecule associated with inflammation, fibrosis, and carcinogenesis.

Keywords: Mitochondria, Nonalcoholic fatty liver disease, Oxidative phosphorylation, Respirometry Bioblast editor: Plangger M O2k-Network Lab: CZ Hradec Kralove Cervinkova Z


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Other 

Organism: Mouse  Tissue;cell: Liver  Preparation: Homogenate 


Coupling state: LEAK, OXPHOS  Pathway: F, N, S, Gp, NS, ROX  HRR: Oxygraph-2k 

Labels, 2020-02