Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/108048
Title: Dual Therapy with Liraglutide and Ghrelin Promotes Brain and Peripheral Energy Metabolism in the R6/2 Mouse Model of Huntington's Disease
Authors: Duarte, Ana I. 
Sjögren, Marie
Santos, Maria S. 
Oliveira, Catarina R. 
Moreira, Paula I. 
Björkqvist, Maria
Issue Date: 12-Jun-2018
Publisher: Springer Nature
Project: Seed Fund from European Huntington’s Disease Network (EHDN) 
Swedish Research Council 
Neuro Sweden 
Kocks Foundation 
PTDC/SAU-TOX/117481/2010 
SFRH/BPD/84473/2012 
European funds from FEDER, through the Programa Operacional Factores de Competitividade – COMPETE 2020 
Serial title, monograph or event: Scientific Reports
Volume: 8
Issue: 1
Abstract: Neuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Combining liraglutide with the orexigenic peptide ghrelin may potentially promote brain/cognitive function in HD. The R6/2 mouse model of HD exhibits progressive central pathology, weight loss, deranged glucose metabolism, skeletal muscle atrophy and altered body composition. In this study, we targeted energy metabolism in R6/2 mice using a co-administration of liraglutide and ghrelin. We investigated their effect on brain cortical hormone-mediated intracellular signalling pathways, metabolic and apoptotic markers, and the impact on motor function in HD. We here demonstrate that liraglutide, alone or together with ghrelin (subcutaneous daily injections of 150 µg/kg (ghrelin) and 0.2 mg/kg (liraglutide), for 2 weeks), normalized glucose homeostatic features in the R6/2 mouse, without substantially affecting body weight or body composition. Liraglutide alone decreased brain cortical active GLP-1 and IGF-1 levels in R6/2 mice, alongside higher ADP levels. Liraglutide plus ghrelin decreased brain insulin, lactate, AMP and cholesterol levels in R6/2 mice. Taken together, our findings encourage further studies targeting energy metabolism in HD.
URI: https://hdl.handle.net/10316/108048
ISSN: 2045-2322
DOI: 10.1038/s41598-018-27121-w
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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