Lipid peroxidation and sphingolipid alterations in the cerebral cortex and hypothalamus of rats fed a high-protein diet.

Objectives. High-protein diets (HPDs) are widely accepted to enhance satiety and energy expenditure and thus have become a popular strategy to lose weight and facilitate muscle protein synthesis. However, long-term high-protein consumption could be linked with metabolic and clinical problems such as renal and liver dysfunctions. This study verified the effects of 8-wk high-protein ingestion on lipid peroxidation and sphingolipid metabolism in the plasma, cerebral cortex, and hypothalamus in rats. Methods. Immunoenzymatic and spectrophotometric methods were applied to assess oxidation-reduction (redox) biomarkers and neutral sphingomyelinase activity, whereas gas-liquid chromatography and high-performance liquid chromatography were used to examine sphingolipid levels. Results. The vast majority of HPD-related alterations was restricted to the hypothalamus. Specifically, an increased rate of lipid peroxidation (increased lipid hydroperoxides, 8-isoprostanes, and thiobarbituric acid reactive substances) associated with ceramide accumulation via the activation of de novo synthesis (decreased sphinganine), salvage pathway (decreased sphingosine), and sphingomyelin hydrolysis (decreased sphingomyelin and...