title: Gastrointestinal dysfunction contributes to weight loss in Huntington's disease mice.
abstract: Weight loss is the most important non-neurological complication of Huntington's disease (HD). It correlates with disease progression and affects the quality of life of HD patients, suggesting that it could be a valuable target for therapeutic intervention. The mechanism underlying weight loss in HD is unknown. Mutant huntingtin, the protein that causes the disease, is not only expressed in the brain, but also along the gastrointestinal (GI) tract. Here we demonstrate that the GI tract of HD mice is affected. At the anatomical level we observed loss of enteric neuropeptides, as well as decreased mucosal thickness and villus length. Exploring the functions of the GI system we found impaired gut motility, diarrhea, and malabsorption of food. The degree of malabsorption was inversely associated with body weight, suggesting that GI dysfunction plays an important role in weight loss in HD mice. In summary, these observations suggest that the GI tract is affected in HD mice and that GI dysfunction contributes to nutritional deficiencies and weight loss.
authors.affiliation: Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, BMC A10, Lund, Sweden. jorienvanderburg@gmail.com
authors.forename: Jorien M M
authors.initials: JM
authors.lastname: van der Burg
authors.forename: Annika
authors.initials: A
authors.lastname: Winqvist
authors.forename: N Ahmad
authors.initials: NA
authors.lastname: Aziz
authors.forename: Marion L C
authors.initials: ML
authors.lastname: Maat-Schieman
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Bates
authors.forename: Patrik
authors.initials: P
authors.lastname: Brundin
authors.forename: Maria
authors.initials: M
authors.lastname: Björkqvist
authors.forename: Nils
authors.initials: N
authors.lastname: Wierup
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D017615:Enteric Nervous System / Q000166:cytology / Q000502:physiology; D005243:Feces / Q000737:chemistry; D005260:Female; D005753:Gastric Mucosa / Q000502:physiology / Q000648:ultrastructure; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000502:physiology; D006816:Huntington Disease / Q000150:complications / Q000503:physiopathology*; D007150:Immunohistochemistry; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000502:physiology / Q000648:ultrastructure; D008286:Malabsorption Syndromes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D014867:Water / Q000378:metabolism; D015431:Weight Loss / Q000502:physiology*
chemical_list: D014867:Water