Treadmill running suppresses the vulnerability of dopamine D2 receptor deficiency to obesity and metabolic complications: a pilot study.

Abstract

Purpose: To investigate the effect of treadmill running on D2R deficiency related susceptibility to high fat diet (HFD )-induced obesity and its metabolic complications.

Methods: D2R-/- and +/- mice were obtained by backcrossing D2R+/- heterozygotes on wild type (WT) littermates (C57BL/6J background) for >10 generations. Mice were randomly assigned to 1) WT mice with standard chow (SC) (WT+SC); 2) WT mice with high-fat diet (WT+HFD); 3) WT mice with high-fat diet plus exercise (WT+HFD+EX), 4) heterozygous (HET) D2R mice with SC (HET+SC); 5) heterozygous D2R mice with HFD (HET+HFD); and 6) heterozygous D2R mice with HFD plus exercise (HET+HFD+EX). In addition, mice assigned to EX groups were subjected to running on a motor-driven rodent treadmill with a frequency of 5 days per week.

Results: After a 10-week HFD treatment, HET D2R (+/-) mice exhibited significantly higher values for hepatic steatosis (p<0.001), areas under the curves (AUCs) for the glucose tolerance test (GTT) and the insulin tolerance test (ITT) (p<0.001 & p<0.001 respectively), serum leptin (p=0.005) and total cholesterol (TC ) (p=0.009), in conjunction with decreased locomotor activity (p=0.031), compared to HET mice exposed to standard chow. However, these HFD-induced elevations in hepatic steatosis (p<0.001), AUCs for GTT and ITT (p=0.032 & p=0.018, respectively), serum leptin (p=0.038) and TC (p=0.038) were significantly alleviated after 10 weeks of treadmill running.

Conclusion: The current findings of the study provide experimental evidence of treadmill running as an effective and non-pharmacologic strategy to treat the susceptibility of brain D2R deficiency to HFD-induced obesity and metabolic disorders.