Dietary fatty acids modulate liver mitochondrial cardiolipin content and its fatty acid composition in rats with non alcoholic fatty liver disease.
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.
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ABSTRACT: Oxidative stress is involved in obesity. However, dietary antioxidants could prevent oxidative stress induced damages. We have previously shown the preventive effects of a melon superoxide dismutase (SODB) on oxidative stress. However, mechanism of action of SODB is still unknown. Here, we evaluated the effects of a 1-month curative supplementation with SODB on the liver of obese hamsters. Golden Syrian hamsters received either a standard diet or a cafeteria diet composed of high-fat, high-sugar and high-salt supermarket products, for 15 weeks. This diet resulted in insulin resistance and in increased oxidative stress in the liver. However, inflammatory markers (IL-6, TNF-α and NF-kB) were not enhanced and no liver steatosis was detected, as usually described in obesity-induced insulin resistance model. After the 1-month supplementation with SODB, body weight and insulin resistance induced by the cafeteria diet were reduced and hepatic oxidative stress corrected. This could be due to the increased expression of the liver antioxidant defence (manganese and copper/zinc superoxide dismutase, catalase and glutathione peroxidase. Even if no inflammation was detected in obese hamsters, inflammatory markers were decreased after SODB supplementation, probably through the reduction of oxidative stress. These findings suggest for the first time that SODB could exert its antioxidant properties by inducing the endogenous antioxidant defence. The mechanisms underlying this induction need to be further investigated.Free Radical Biology & Medicine 06/2013; · 5.27 Impact Factor
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ABSTRACT: The interaction of dietary fats and carbohydrates on liver mitochondria were examined in male FBNF1 rats fed 20 different low-fat, isocaloric diets. Animal growth rates and mitochondrial respiratory parameters were essentially unaffected, but mass spectrometry-based, mitochondrial lipidomics profiling revealed increased levels of cardiolipins (CLs), a family of phospholipids essential for mitochondrial structure and function, in rats fed saturated or trans fat-based diets with a high glycemic index. These mitochondria showed elevated monolysocardiolipins (a CL precursor/product of CL degradation), elevated ratio of trans PC (18:1/18:1) to cis PC (18:1/18:1) (a marker of thiyl radical stress), and decreased ubiquinone Q9 -- the latter two of which imply a low-grade mitochondrial redox abnormality. Extended analysis demonstrated: (i) dietary fats and, to a lesser extent, carbohydrates induce changes in the relative abundance of specific CL species; (ii) Fatty acid (FA) incorporation into mature CLs undergoes both positive (>400-fold) and negative (2.5-fold) regulation; and, (iii) dietary lipid abundance and incorporation of FAs into both the CL pool and specific mature tetra-acyl CLs are inversely related, suggesting previously unobserved compensatory regulation. This study reveals previously unobserved complexity/regulation of the central lipid in mitochondrial metabolism.The Journal of Lipid Research 05/2013; · 4.39 Impact Factor
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ABSTRACT: The incidence of metabolic syndrome components including obesity, lipid deregulation, insulin resistance (IR) and non-alcoholic fatty liver disease is increasing rapidly in wealthy societies. The present study was designed to determine the effect of different nutritional lipid patterns (quantity and quality) on lipid utilisation and oxidative stress in the liver and muscle of rats in an integrated fashion. A total of forty-eight Wistar male rats were fed for 12 weeks with a mixed, lard or fish-oil diet, containing either 50 or 300 g lipid/kg. Rats developed liver steatosis associated with moderate liver injury when fed the 30 % lipid diets, in spite of the absence of overt obesity or IR, except when fed the lard 30 % lipid diet. The intake of the 30 % lipid diets decreased hepatic lipogenesis and mitochondriogenesis and increased lipid peroxidation and protein oxidation. Surprisingly, muscle lipid content was not modified whatever the administered diet. The intake of the 30 % lipid diets increased the muscle protein expression of fatty acid (FA) translocase/cluster of differentiation 36 (FAT/CD36), PPARγ co-activator 1α (PGC-1α) and muscle carnitine palmitoyltransferase 1 (m-CPT1), reflecting increased FA transport in the muscle associated with increased oxidative metabolism. The lard 30 % lipid diet led to IR without modifying the muscle lipid content. The fish-oil 30 % lipid diet failed to prevent the development of hepatic steatosis and made the tissues more prone to oxidation. Overall, the present study suggests that the FA composition of muscle is more important than lipid accumulation itself in the modulation of insulin sensitivity, and indicates that precaution should be taken when advising an unphysiologically high (pharmacological) supplementation with long-chain n-3 PUFA.The British journal of nutrition 05/2013; · 3.45 Impact Factor