Investigation of brain acylcarnitine profile in rats with streptozotocin-induced diabetes

Objective: Diabetes is a systemic disease that affects not only peripheral tissues but also the central nervous system metabolism. . In this study, the aim is to evaluate the brain acylcarnitine profile in an experimental diabetic rat model induced by STZ based on gender. By revealing changes in acylcarnitine levels in brain tissue between control and diabetic groups, the study aimed to understand the effects of diabetes on brain metabolism and identify potential biomarkers for elucidating the pathophysiology of diabetes. Materials and Methods: A total of 20 Wistar albino rats (10 female, 10 male) were divided into four groups; one female rat was lost after STZ (40 mg/kg, i.p.) administration, and analyses were performed on 19 rats. The experiment lasted 29 days, during which water and feed consumption, body weight, and blood glucose levels were monitored. After sacrifice, hippocampal tissues were collected and samples were analyzed using an LC-MS/MS device. Classical statistical methods and the MetaboAnalyst platform were used for metabolomic data analysis. Results: Glucose levels were significantly elevated in diabetic groups, while weight gain was suppressed. Metabolomic analyses revealed that short-chain carnitines such as C0, C3, and C5:1 were significantly reduced in diabetic rats, whereas medium- and long-chain carnitines such as C8, C14:2, and C18:2 were increased. PCA analysis provided partial differentiation between groups with the first five components explaining 82% of the variance; in VIP score analysis, C3 and C5:1 stood out for their discriminatory power. According to the volcano plot analysis, a significant increase was detected in C8 and C4 metabolites in the diabetic male group compared to the male control group, while a marked decrease was observed in C10 levels. In diabetic female rats, the Fold Change analysis compared to the female control group revealed a significant increase in C8 and C12 levels, while a marked decrease was observed in C4 levels. In gender-based analyses, it was determined that some metabolite levels were higher in diabetic male rats than in females, and it was suggested that this difference may be related to hormonal/metabolic causes. Conclusion: In the streptozotocin-induced diabetic rat model, the acylcarnitine profile of the hippocampus region showed significant changes based on both gender and group. These differences in short-, medium-, and long-chain acylcarnitine levels were interpreted as reflecting mitochondrial dysfunction, as well as impairments in lipid and amino acid metabolism and glucose utilization. The study results suggest that compounds such as C0, C3, and C5:1 may serve as potential biomarkers in understanding the pathophysiology of diabetes and provide a foundation for new research at the neurometabolic level.