High fat diet feeding induced insulin resistance exacerbates 6-OHDA mediated neurotoxicity and behavioral abnormalities in rats

Some of the clinical reports suggest that insulin resistance could be a risk factor for Parkinson's disease (PD) development, however experimental data is scarce. Our previous work has suggested that insulin resistance could be an important factor that leads to diabetes associated neurodegeneration. In the present study, we evaluated whether insulin resistance is linked to PD pathology or not. For this purpose, we first standardized an animal model which could mimic the co-morbid insulin resistance and PD condition. For development of insulin resistance, we fed the male Wistar rats with high fat diet (HFD) for eight weeks, followed by 6-hydroxydopamine (6-OHDA) administration, a toxin widely used for PD induction, in medial forebrain bundle (MFB) of rats. The 6-OHDA treatment resulted in neuronal damage and loss of striatal dopamine level. This dopamine loss was correlated with impaired performance in behavioral tasks such as rotarod, narrow beam walk test and locomotor activity. Interestingly, we found that exposure to HFD exacerbated the effects of 6-OHDA on striatal dopamine loss and behavioral parameters in rats, indicating that HFD-induced insulin resistance is associated with a diminished capacity of dopaminergic neurons to cope with 6-OHDA mediated neurotoxicity. Based upon these findings, it can be suggested that HFD feeding induced insulin resistance exacerbates the PD pathology.