4.5 Article

The mitochondrial-targeted antioxidant, MitoQ, increases liver mitochondrial cardiolipin content in obesogenic diet-fed rats

Journal

BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
Volume 1847, Issue 10, Pages 1025-1035

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbabio.2015.05.019

Keywords

Cardiolipin; Fatty acids; Hepatic steatosis; High fat diet; Mitochondria; Phospholipids

Funding

  1. COST Action CM1201 Biomimetic Radical Chemistry [MoU COST 4119/12]
  2. French Lipid Nutrition Group
  3. National Institute for Agronomic Research
  4. Human nutrition Department (Alim-H department)
  5. MRC [MC_U105663142] Funding Source: UKRI
  6. Medical Research Council [MC_U105663142] Funding Source: researchfish

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Cardiolipin (CL), a unique mitochondrial phospholipid, plays a key role in several processes of mitochondrial bioenergetics as well as in mitochondrial membrane stability and dynamics. The present study was designed to determine the effect of MitoQ a mitochondrial-targeted antioxidant, on the content of liver mitochondrial membrane phospholipids, in particular CL, and its fatty acid composition in obesogenic diet-fed rats. To do this, twenty-four 6 week old male Sprague Dawley rats were randomized into three groups of 8 animals and fed for 8 weeks with either a control diet, a high fat diet (HF), or a HF diet with MitoQ (HF + MitoQ). Phospholipid classes and fatty acid composition were assayed by chromatographic methods in liver and liver mitochondria. Mitochondrial bioenergetic function was also evaluated. While MitoQ had no or slight effects on total liver fatty acid composition and phospholipid classes and their fatty add composition, it had major effects on liver mitochondrial phospholipids and mitochondrial function. Indeed, MitoQ both increased CL synthase gene expression and CL content of liver mitochondria and increased 18:2n-6 (linoleic add) content of mitochondrial phospholipids by comparison to the HF diet. Moreover, mitochondrial CL content was positively correlated to mitochondrial membrane fluidity, membrane potential and respiration, as well as to ATP synthase activity, while it was negatively correlated to mitochondrial ROS production. These findings suggest that MitoQ may decrease pathogenic alterations to CL content and profiles, thereby preserving mitochondrial function and attenuating the development of some of the features of metabolic syndrome in obesogenic diet-fed rats. (C) 2015 Elsevier B.V. All rights reserved.

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