Dietary fatty acids modulate liver mitochondrial cardiolipin content and its fatty acid composition in rats with non alcoholic fatty liver disease.

INRA UMR 866, Dynamique Musculaire et Métabolisme, 34060, Montpellier, France.
Journal of Bioenergetics (Impact Factor: 2.71). 06/2012; 44(4):439-52. DOI: 10.1007/s10863-012-9448-x
Source: PubMed

ABSTRACT No data are reported on changes in mitochondrial membrane phospholipids in non-alcoholic fatty liver disease. We determined the content of mitochondrial membrane phospholipids from rats with non alcoholic liver steatosis, with a particular attention for cardiolipin (CL) content and its fatty acid composition, and their relation with the activity of the mitochondrial respiratory chain complexes. Different dietary fatty acid patterns leading to steatosis were explored. With high-fat diet, moderate macrosteatosis was observed and the liver mitochondrial phospholipid class distribution and CL fatty acids composition were modified. Indeed, both CL content and its C18:2n-6 content were increased with liver steatosis. Moreover, mitochondrial ATP synthase activity was positively correlated to the total CL content in liver phospholipid and to CL C18:2n-6 content while other complexes activity were negatively correlated to total CL content and/or CL C18:2n-6 content of liver mitochondria. The lard-rich diet increased liver CL synthase gene expression while the fish oil-rich diet increased the (n-3) polyunsaturated fatty acids content in CL. Thus, the diet may be a significant determinant of both the phospholipid class content and the fatty acid composition of liver mitochondrial membrane, and the activities of some of the respiratory chain complex enzymes may be influenced by dietary lipid amount in particular via modification of the CL content and fatty acid composition in phospholipid.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Mitochondrial membrane lipid composition is a critical factor in non-alcoholic steatohepatitis (NASH). Exercise is the most prescribed therapeutic strategy against NASH and a potential modulator of lipid membrane. Thus, we aimed to analyze whether physical exercise exerted preventive (voluntary physical activity-VPA) and therapeutic (endurance training-ET) effect on NASH-induced mitochondrial membrane changes. Sprague-Dawley rats (n=36) were divided into standard-diet sedentary (SS, n=12), standard-diet VPA (SVPA, n=6), high-fat diet sedentary (HS, n=12) and high-fat diet VPA (HVPA, n=6). After 9 weeks of diet-specific feeding, half of SS and HS group were engaged in an ET program for 8 weeks/5d/week/1h/day (SET, HET). Liver mitochondria were isolated for oxygen consumption and transmembrane-electric potential (ΔΨ) assays. Mitochondrial phospholipid classes and fatty acids were quantified through thin layer chromatography and gas chromatography, respectively, while cardiolipin (CL), phosphatidylcholine (PC) phosphatidylethanolamine (PE) and phosphatidylinositol (PI) molecular profile was determined by electrospray mass spectrometry. In parallel with histological signs of NASH, high-fat diet decreased PI, CL and PC/PE ratio, whereas PE and phosphatidic acid content increased in sedentary animals (HS vs. SS). Moreover, a decrease in linolelaidic, monounsaturated fatty acids content and an increase in saturated fatty acids (SFAS) were observed. Along with phospholipidomic alterations, HS animals showed a decrease in respiratory control ratio (RCR), ΔΨ and FCCP-induced uncoupling respiration (HS vs. SS). Both phospholipidomic (PC/PE, SFAS) and mitochondrial respiratory alterations were counteracted by exercise interventions. Exercise used as preventive (VPA) or therapeutic (ET) strategies preserved liver mitochondrial phospholipidomic profile and maintained mitochondrial function in a model of NASH.
    The International Journal of Biochemistry & Cell Biology 07/2014; 54:163-173. DOI:10.1016/j.biocel.2014.07.011 · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Excessive dietary lipid intake, coupled with lack of exercise, are the major causes of the development and progression of metabolic syndrome features e. g. obesity, hepatic steatosis, insulin resistance, type 2 diabetes and cardiovascular diseases. These metabolic diseases are associated with both structural and functional alterations of mitochondria. Cardiolipin (CL) is a unique phospholipid that is almost exclusively localized in the mitochondrial inner membrane. Cardiolipin is at the heart of mitochondrial metabolism playing a key role in several processes of mitochondrial bioenergetics as well as in mitochondrial membrane stability and dynamics, and in many of the mitochondrial-dependent steps of apoptosis. Indeed, alterations to CL content and acyl chain profile have been associated with mitochondrial dysfunction in multiple tissues in Barth syndrome and in many other physio-pathological conditions. After a brief overview of the biological roles of CL, we highlight the consequences of lipid overload-related nutritional manipulations as well as related metabolic disorders on both CL content and its fatty acid composition in the major metabolic tissues, the heart, muscle and liver. The goal of this review is to fill a void in the CL literature concerning the effects of CL abundance and form that arise following high lipid supplementation and the related metabolic disorders.
    Journal of Bioenergetics 06/2014; 46(5). DOI:10.1007/s10863-014-9555-y · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The prevalence of metabolic syndrome components including obesity, dyslipidemia, insulin resistance and hepatic steatosis is rapidly increasing in wealthy societies. It is accepted that inflammation/oxidative stress are involved in the initiation/evolution of the metabolic syndrome features. The present work was designed to evaluate the effects of three major cellular ROS production systems on obesity, glucose tolerance and hepatic steatosis development and on oxidative stress onset. To do so, forty young male Sprague Dawley rats were divided into 5 groups: 1-control group, 2-high fat (HF) group (60% energy from fat), 3-HF+MitoQ (mitochondrial ROS scavenger), 4-HF+Apocynin (NADPH oxidase inhibitor), 5-HF+Allopurinol (xanthine oxidase inhibitor). After 8 weeks of these treatments, surrogate metabolic syndrome, mitochondrial function and oxidative stress markers were measured in blood and liver. As expected, rats fed the high fat diet exhibited increased body weight, glucose intolerance, overt hepatic steatosis and increased hepatic oxidative stress. The impacts of the studied ROS inhibitors on these aspects of the metabolic syndrome were markedly different. MitoQ showed the most clinically relevant effects, attenuating body weight gain and glucose intolerance provoked by the HF diet. Both Apocynin and Allopurinol showed limited effects suggesting secondary roles of xanthine oxidase or NADPH oxidase-dependent ROS production in the onset of oxidative stress-dependent obesity, glucose intolerance and hepatic steatosis process. Thus, MitoQ revealed the central role of mitochondrial oxidative stress in the development of metabolic syndrome and suggested that mitochondria-targeted antioxidants may be worth considering as potentially helpful therapies for metabolic syndrome features.
    Free Radical Research 07/2014; DOI:10.3109/10715762.2014.945079 · 2.99 Impact Factor