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 increased neutral sphingomyelinase activity) was noted.

Conclusions: This study showed that HPD substantially affected hypothalamic metabolic pathways, which potentially alter cerebral output signals to the peripheral tissues.