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Lucienne, M.* ; Gerlini, R. ; Rathkolb, B. ; Calzada-Wack, J. ; Forny, P.* ; Wueest, S.* ; Kaech, A.* ; Traversi, F.* ; Forny, M.* ; Bürer, C.* ; Aguilar-Pimentel, J.A. ; Irmler, M. ; Beckers, J. ; Sauer, S.* ; Kölker, S.* ; Dewulf, J.P.* ; Bommer, G.T.* ; Hoces, D.* ; Gailus-Durner, V. ; Fuchs, H. ; Rozman, J. ; Froese, D.S.* ; Baumgartner, M.R.* ; Hrabě de Angelis, M.

Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria.

Hum. Mol. Genet. 32, 2717-2734 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Green as soon as Postprint is submitted to ZB.
Inherited disorders of mitochondrial metabolism, including isolated methylmalonic aciduria, present unique challenges to energetic homeostasis by disrupting energy-producing pathways. To better understand global responses to energy shortage, we investigated a hemizygous mouse model of methylmalonyl-CoA mutase (Mmut)-type methylmalonic aciduria. We found Mmut mutant mice to have reduced appetite, energy expenditure and body mass compared with littermate controls, along with a relative reduction in lean mass but increase in fat mass. Brown adipose tissue showed a process of whitening, in line with lower body surface temperature and lesser ability to cope with cold challenge. Mutant mice had dysregulated plasma glucose, delayed glucose clearance and a lesser ability to regulate energy sources when switching from the fed to fasted state, while liver investigations indicated metabolite accumulation and altered expression of peroxisome proliferator-activated receptor and Fgf21-controlled pathways. Together, these shed light on the mechanisms and adaptations behind energy imbalance in methylmalonic aciduria and provide insight into metabolic responses to chronic energy shortage, which may have important implications for disease understanding and patient management.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Multiple Oxphos Deficiency; Ppar-alpha; Insulin-resistance; Mitochondrial Dysfunction; Body-temperature; Lipid-metabolism; Adipose-tissue; Brown Fat; Liver; Fgf21
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Journal Human Molecular Genetics
Quellenangaben Volume: 32, Issue: 17, Pages: 2717-2734 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)