Long-term dietary protein intake affects uncoupling protein mRNA gene expression in liver and muscle of rats

An increased amino acid oxidation during high protein intake was hypothesized to contribute to enhanced mitochondrial oxygen radical generation resulting in oxidative stress. Thus, we measured markers of oxidative stress (liver lipid peroxide concentrations, protein carbonyl concentrations in plasma, total liver and blood glutathione concentration) in rats fed high protein diets. Groups of adult rats were adapted (18 wk) to diets containing either 13.8%, (AP), 25.7% (MP) or 51.3% (HP) casein. A fourth group received a HP diet lacking the antioxidative protection factor vitamin E in the vitamin mixture (HP-E) for comparison purposes. Higher concentrations of plasma protein carbonyls and liver lipid peroxides were determined in rats fed the AP and the HP-E diets compared with those fed the MP and HP diets. Total glutathione concentrations in liver were significantly lower in rats fed the AP diet compared with MP, HP and HP-E groups. Therefore, a long-term intake of high protein diets did not necessarily result in oxidative stress. This led us to suggest that proton leak mediated by mitochondrial uncoupling proteins (UCP) might prevent oxidative stress during high protein intake. UCP2 mRNA expression in liver correlated positively with the dietary protein intake. Highest mean values were found in vitamin E deficient rats. In skeletal muscle mRNA expression of UCP2 was significantly lower in MP group as compared to AP and HP groups. UCP3 mRNA expression in skeletal muscle showed a similar pattern but was not significantly different between diet groups. A positive correlation was calculated between UCP2 mRNA expression in both liver and skeletal muscle and lipid peroxide concentrations in liver. Our results indicate that UCP2 mRNA expression in liver is dependent on the level of dietary protein intake and provide evidence for a role of UCP2 in the control of reactive oxygen species during substrate oxidation and protection against dietary induced oxidative stress.