Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington's Disease Mouse Model R6/2

PLoS Curr. 2015 Apr 20:7:ecurrents.hd.019b33aae1c519e6e8b68e7cf3e7818e. doi: 10.1371/currents.hd.019b33aae1c519e6e8b68e7cf3e7818e.

Abstract

Huntington's disease (HD) is a neurodegenerative illness, where selective neuronal loss in the brain caused by expression of mutant huntingtin protein leads to motor dysfunction and cognitive decline in addition to peripheral metabolic changes. In this study we confirm our previous observation of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indicating a potential to explore this defect in a biomarker context. Moreover, R6/2 animals displayed lower blood glucose levels during prolonged fasting compared to wild type animals.

Grants and funding

This study was supported by the University of Copenhagen and Signe and Peter Gregersens Mindefond. The sponsors of this study had no role in study design, data collection, analysis, interpretation, or writing of the report. The authors declare no conflict of interest in study undertaken.