Peripheral and cerebral metabolic features in an animal model of Huntington's disease

Metabolic dysfunction is relatively common in Huntington's disease (HD) patients and in HD transgenic mouse models. The YAC128 mice express full-length mutant huntingtin (mHtt) with 128 glutamines and manifest a phenotype close to HD patients. The objective of our study was to evaluate the effect of an hyperglycemic background on peripheral and central metabolic parameters in YAC128 mice versus wild-type littermates. Both YAC128 and WT mice exhibited elevated fasting and non-fasting plasma glucose levels, but no significant change in body weight or metabolic parameters were found. However, in Insulin Tolerance Test, YAC128 mice showed significantly higher glucose values, compared to WT mice. The HD mice also showed a tendency to impairment in motor coordination and balance. In YAC128 mice, plasma or brain levels of IGF-1 and insulin were not significantly changed, although there was a tendency for a decrease in insulin. Moreover, a reduction in energy charge and higher lactate/pyruvate ratio were detected in HD brain. These data suggest that expression of full-length mHtt in hyperglycémie background may induce both peripheral and central metabolic changes.