Peripheral Expression of Mutant Huntingtin is a Critical Determinant of Weight Loss and Metabolic Disturbances in Huntington's Disease.

ABSTRACT: Deteriorating weight loss in patients with Huntington's disease (HD) is a complicated peripheral manifestation and the cause remains poorly understood. Studies suggest that body weight strongly influences the clinical progression rate of HD and thereby offers a valuable target for therapeutic interventions. Mutant huntingtin (mHTT) is ubiquitously expressed and could induce toxicity by directly acting in the peripheral tissues. We investigated the effects of selective expression of mHTT exon1 in fat body (FB; functionally equivalent to human adipose tissue and liver) using transgenic Drosophila. We find that FB-autonomous expression of mHTT exon1 is intrinsically toxic and causes chronic weight loss in the flies despite progressive hyperphagia, and early adult death. Moreover, flies exhibi

SUBMITTER: Lakra P 

PROVIDER: S-EPMC6626032 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature