title: Altered lipid metabolism in Drosophila model of Huntington's disease.
abstract: Huntington's disease (HD) is late-onset, progressive neurodegenerative disorder caused by expansion of polyglutamine (polyQ) repeat within Huntingtin (Htt) protein. In HD patients, energy-related manifestations such as modulation of weight during entire course of disease with energy deficit at terminal stage have been reported, however, underlying reason remains elusive till date. Lipids, carbohydrate and protein constitute a predominant fraction of body's energy reservoir and perturbation in their homeostasis may influence weight. To discern role of these energy molecules in weight alteration, we quantified them in an in vivo transgenic Drosophila model of HD. We document that diseased flies exhibit change in weight due to an altered lipid metabolism, as evident from considerably high lipid levels at the time of disease onset followed by a pathologic decline at end-stage. An alteration in intracellular lipid droplet size suggested altered cellular lipid turnover. Furthermore, diseased flies displayed substantial changes in carbohydrate and protein content. Interestingly, alteration in weight and lipid levels are independent of the feeding pattern in diseased condition and exhibit weak correlation with insulin-like peptide or adipokinetic hormone producing cells. We propose that therapeutic intervention aimed at restoring lipid levels and associated metabolic pathways may improve longevity and quality of patient's life.
authors: Department of Zoology, University of Delhi, Delhi, 110007, India.
authors: Kumari
authors: K
authors: Aditi
authors: Department of Zoology, University of Delhi, Delhi, 110007, India.
authors: Mallikarjun N
authors: MN
authors: Shakarad
authors: Department of Zoology, University of Delhi, Delhi, 110007, India.
authors: Namita
authors: N
authors: Agrawal
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001835:Body Weight; D002490:Central Nervous System / Q000378:metabolism; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics* / Q000378:metabolism; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D009154:Mutation; D017933:Peripheral Nervous System / Q000378:metabolism
chemical_list: D054392:Adipokines; D029721:Drosophila Proteins; C542005:Htt protein, Drosophila; D000071058:Huntingtin Protein