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Endocrine Abstracts (2012) 29 P554

Diabetes

High-fructose diet, an animal model of insulin resistance, causes mitochondrial dysfunction by altering the activity of respiratory chain complex I

C Sánchez-Martín1, M Sanz1,2, D Detaille3, J Recio-Córdova1, F Peralta4 & G R-Villanueva1

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1University of Salamanca, Salamanca, Spain; 2Institut Cochin, INSERM U-1016, Paris, France; 3INSERM U884, Université Joseph Fourier, Grenoble, France; 4Nuestra Señora de Sonsoles Hospital, Avila, Spain.


Introduction: The current epidemic of Type 2 Diabetes Mellitus (T2DM) and obesity is positively correlated with a rise in consumption of high-fructose syrups and refined carbohydrates. Recent reports have showed that feeding rodent a high-fructose diet leads to insulin resistance, glucose intolerance and dyslipidaemia. Nevertheless, its mitochondrial effects has not been fully studied yet.

Aim: We decided to explore the alterations in mitochondrial bioenergetics induced in high-fructose fed rats, as well as the underlying mechanisms.

Materials and methods: Male Wistar rats were separated in two different groups and received either a standard diet or the high-fructose diet during 6 weeks. Liver mitochondria were isolated from fed animals by standard differential centrifugation. Oxygen consumption rates were measured at 30 °C using a Clark-type oxygen electrode whereas ROS production was assayed by incubating mitochondria in a stirred 2 ml volume with 10 UI horseradish peroxidase and 2 μM Amplex Red. Moreover, the activity of mitochondrial respiratory chain complexes I, II and III were spectrophotometrically determined.

Results: High-fructose diet inhibited oxygen consumption (JO2) when glutamate and malate (GM) or succinate and malate (SM) were used as energetic substrate. This inhibition affected the state three of respiration (in the presence of ADP) and the uncoupled state (after addition of dinitrophenol). On the other hand, after addition of rotenone that stimulates ROS production in presence of GM, mitochondria isolated from fructose-fed rats showed lower ROS production. By using SM as respiratory substrate, high-fructose diet also reduced ROS production. Finally, we found that complex I activity was significantly inhibited by feeding a high-fructose diet.

Conclusions: Our data show that high-fructose diet diminishes respiratory complex I activity leading to a reduction of both ROS production and mitochondrial respiration. This new finding could contribute to the knowledge of the mechanisms involved in mitochondrial dysfunction in type two diabetes.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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