Long-term consumption of high-fat diet impairs motor coordination without affecting the general motor activity

Abstract

Consumption of affordable food that is rich in fat and carbohydrates has increased over the last few decades. As such, high caloric intake and weight gain contribute to sedentary lifestyle. The aim of this study was to investigate the long-term effect of food reach in fat on motor function and dopaminergic system. In the present study, six-week old male C57bl/6 mice were fed either high-fat diet (HFD) or regular chow diet (RD) for 15 months, followed by estimation of spontaneous locomotor activity, body composition, assessment of metabolic outcomes, and histological examination of dopaminergic neurodegeneration. Although body weight stayed similar in both diet-fed mice, HFD-fed mice had decreased lean tissue mass and increased fat mass. In particular, isolation of fat depots showed that HFD-fed mice had increased brown, retroperitoneal and subcutaneous fat mass, in comparison to WT mice. Reduced lean tissue did not influence the muscle strength as it was shown by grid test. The HFD intake did not affect the spontaneous locomotor activity. However, HFD-fed mice displayed time-dependent reduction in motor coordinative skills measured by rotarod, and this was further confirmed by pole test, stepping test and hind-limb clasping test towards the end of in vivo studies. Reduction in coordinative abilities of HFD-fed mice was accompanied by impaired glucose tolerance test, elevated blood insulin and leptin levels. Histological data showed that HFD consumption did not induce loss of tyrosine hydroxylase (TH)-positive dopamine neurons, nor increased number of activated CD68-positive microglia cells in substantia nigra (SN). Taken together, these data suggest that adiposity and insulin resistance induced with HFD consumption led to reduced motor coordination.