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Hypothalamic mitochondrial dysfunction associated with anorexia in the anx/anx mouse
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2011 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 44, 18108-18113 p.Article in journal (Refereed) Published
Abstract [en]

The anorectic anx/anx mouse exhibits disturbed feeding behavior and aberrances, including neurodegeneration, in peptidergic neurons in the appetite regulating hypothalamic arcuate nucleus. Poor feeding in infants, as well as neurodegeneration, are common phenotypes in human disorders caused by dysfunction of the mitochondrial oxidative phosphorylation system (OXPHOS). We therefore hypothesized that the anorexia and degenerative phenotypes in the anx/anx mouse could be related to defects in the OXPHOS. In this study, we found reduced efficiency of hypothalamic OXPHOS complex I assembly and activity in the anx/anx mouse. We also recorded signs of increased oxidative stress in anx/anx hypothalamus, possibly as an effect of the decreased hypothalamic levels of fully assembled complex I, that were demonstrated by native Western blots. Furthermore, the Ndufaf1 gene, encoding a complex I assembly factor, was genetically mapped to the anx interval and found to be down-regulated in anx/anx mice. These results suggest that the anorexia and hypothalamic neurodegeneration of the anx/anx mouse are associated with dysfunction of mitochondrial complex I.

Place, publisher, year, edition, pages
2011. Vol. 108, no 44, 18108-18113 p.
Keyword [en]
neuropeptides, reactive oxygen species, agouti-gene related protein, food intake, neuroinflammation
National Category
Medical Biotechnology
URN: urn:nbn:se:kth:diva-50835DOI: 10.1073/pnas.1114863108ISI: 000296373400050OAI: diva2:462864
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
QC 20111208Available from: 2011-12-08 Created: 2011-12-08 Last updated: 2011-12-08Bibliographically approved

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Uhlén, Mathias
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ProteomicsAlbanova VinnExcellence Center for Protein Technology, ProNova
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