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Nutrition and Disease

Liver Carbohydrate and Lipid Metabolism of Insulin-Deficient Mice Is Altered by trans-10, cis-12 Conjugated Linoleic Acid^1,2

Unité Mixte de Recherche 866 INSERM-Université de Bourgogne, Equipe physiopathologie des dyslipidémies, Faculté des Sciences Gabriel, 21000 Dijon, France

Feeding mice the trans-10, cis-12 (t10c12) conjugated linoleic acid (CLA) isomer is associated with lipodystrophy, insulin resistance, hyperinsulinemia, and liver steatosis. It has been hypothesized that CLA-induced liver steatosis is the result of increased hepatic lipogenesis stimulated by high insulin levels. We studied the effects of a 12-d t10c12CLA treatment (1 g/100 g diet) on liver carbohydrate and lipid metabolism in control and streptozotocin (STZ)-injected mice. STZ mice were characterized by insulin deficiency, hypertriglyceridemia, and depletion of liver triglyceride and glycogen. Remarkably, feeding t10c12CLA to diabetic mice (STZ-CLA) normalized these variables. Reconstitution of fat stores in the livers of STZ-CLA mice was associated with lower fatty acid (FA) oxidation rates and greater malonyl-CoA concentration than in STZ mice. FA translocase and VLDL receptor mRNA levels were greater in STZ-CLA than in STZ mice, suggesting that t10c12CLA increased liver lipid uptake. Phosphoenolpyruvate carboxykinase mRNA levels and AMP kinase phosphorylation were lower in STZ-CLA than in STZ mice, indicating that t10c12CLA may reduce glucogenic activity and promote glycogenesis in diabetic mice. Because glycemia and glucokinase expression were not modified by t10c12CLA treatment, we postulated that glycogen accumulation is likely not the result of an effect of t10c12CLA on plasma glucose utilization, but rather is due to the contribution of lactate, the concentration of which was higher in muscle of STZ-CLA mice. The results demonstrate that t10c12CLA stimulates liver lipid accumulation in the absence of insulin and, thus, suggest that t10c12CLA can improve liver carbohydrate and lipid metabolism in type I diabetic mice.

^* To whom correspondence should be addressed. E-mail: pascal.degrace{at}u-bourgogne.fr.

Manuscript received 3 June 2009. Initial review completed 30 June 2009. Revision accepted 24 July 2009.

Published online 19 August 2009.