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Biochim Biophys Acta. 2015 Oct;1847(10):1025-35. doi: 10.1016/j.bbabio.2015.05.019. Epub 2015 May 28.

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

Author information

1
INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060 Montpellier, France.
2
ISOF Bio Free Radicals, Bologna, Italy.
3
CIRAD, UMR IATE, F-34398 Montpellier, France.
4
MRC Mitochondrial Biology Unit, MRC Building, Hills Road, Cambridge CB2 0XY, UK.
5
Institute of Nanoscience & Nanotechnology, National Center of Scientific Research "Demokritos", Patriarchou Gregoriou Street, 15310, Agia Paraskevi, Athens, Greece.
6
Montpellier SupAgro, UMR IATE, F-34060 Montpellier, France.
7
INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060 Montpellier, France. Electronic address: cfeillet@supagro.inra.fr.

Abstract

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 6week old male Sprague Dawley rats were randomized into three groups of 8 animals and fed for 8weeks 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 acid 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 acid) 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.

KEYWORDS:

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

PMID:
26028302
DOI:
10.1016/j.bbabio.2015.05.019
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