Hyperglycemia Alters Lipid Metabolism and Ultrastructural Morphology of Cerebellum in Brains of Diabetic Rats: Therapeutic Potential of Raffia Palm (Raphia hookeri G. Mann & H. Wendl) Wine

The present study investigated the effect of raffia palm (Raphia hookeri) wine (RPW) on hyperglycemia-mediated lipid metabolites and pathways, functional chemistry and ultrastructural morphology of cerebellums in type 2 diabetes (T2D). T2D was induced in male Sprague-Dawley rats by feeding with 10% fructose ad libitum for 2 weeks before injecting intraperitoneally with 40 mg/kg bodyweight (bw) streptozotocin. Following confirmation of hyperglycemia at blood glucose >200 mg/dL, diabetic rats were treated with RPW at 150 and 300 mg/kg bw respectively. Metformin served as the standard drug. Negative and normal controls consisted of untreated diabetic and non-diabetic rats, respectively. After 5 weeks of treatment, the rats were humanely sacrificed, and their cerebellum excised from the harvested brains. GC-MS analysis revealed significant alterations in cerebellar lipid metabolites depicted by changes in unsaturated and saturated fatty acids, fatty - esters, alcohols, and amides, glycols and steroids on induction of T2D. Pathway enrichment analysis of the lipid metabolites revealed inactivation of arachidonic metabolic pathway following T2D induction. Treatment with both doses of RPW restored most of the metabolites, while reactivating arachidonic acid metabolism (high dose only). Low dose of RPW led to the activation of retinol metabolism. Both doses of RPW maintained cerebellar functional chemistry as revealed by FTIR analysis. TEM analysis revealed swollen mitochondria, depleted numbers of synaptic vesicles, and shrunk synaptic clefts following induction of T2D. These ultrastructural morphologies were improved in RPW-treated rats. These results portray the therapeutic potential of raffia palm wine in the management of neurodegenerative complications in T2D.

Keywords: Cerebellum; Metabolomics; Type 2 diabetes; and Ultrastructural morphology.