Protective effect of grape seed and skin extract against high-fat diet-induced dyshomeostasis of energetic metabolism in rat lung.

BACKGROUND: Obesity is currently one of the major epidemics of this millennium and affects poeples throughout the world. It causes multiple systemic complications as it significantly interferes with respiratory function. OBJECTIVE: We aimed in the present work to study the effect of high fat diet (HFD) on lung oxidative stress and energy metabolism alterations, as well as the putative protection afforded by grape seed and skin extract (GSSE). METHODS: We started by characterizing the GSSE and its composition using gas chromatography coupled to mass spectrometry (GC-MS). We used a rat model of high-fat-diet and we evaluated the effect of GSSE on oxidative stress and energetic disturbances induced by HFD. We analyzed the effect of HFD on lung oxidative status by assessing lipid oxidation level, non-protein thiols (NPSH) and superoxide anion level… We also evaluated the effect of HFD on creatine kinase (CK), malate dehydrogenase (MDH) and mitochondrial complex IV. RESULTS: HFD induced body weight gain, increased lung weight and lipid content without affecting insulinemia and dropped adiponectemia. HFD also provoked on lung oxidative stress characterized by increased carbonylation (+ 95%; p = 0.0045), decreased of NPSH (- 32%; p = 0.0291) and inhibition of antioxidant enzyme activities such as glutathione peroxidase (- 25%; p = 0.0074). HFD also altered lung intracellular mediators as superoxide anion O2¯ (+ 59%; p = 0.0027) and increased lung xanthine oxidase activity (+ 27%; p = 0.0122). HFD induced copper depletion (- 24%; p = 0.0498) and lead (- 51%: p = 0.0490) from the lung. Correlatively HFD decreased the copper associated enzyme tyrosinase (- 29%; p = 0.0500) and decreased glutamine synthetase activity (- 31%; p = 0.0027). HFD altered also lung energy metabolism by increasing CK activity (+ 22%; p = 0.0108) and decreasing MDH and mitochondrial complex IV activities (- 28%; p = 0.0120, - 31%; p = 0.0086 respectively). Importantly all these alterations were efficiently corrected with GSSE treatment. CONCLUSION: In conclusion, GSSE has the potential to alleviate the deleterious lipotoxic effect of HFD on lung and it could find potential application in the protection against HFD-induced lung complications.