Allostatic hypermetabolic response in PGC1 alpha/beta heterozygote mouse despite mitochondrial defects
dc.contributor.author | Rodriguez- Cuenca, Sergio | |
dc.contributor.author | Lelliot, Christopher J. | |
dc.contributor.author | Campbell, Mark | |
dc.contributor.author | Peddinti, Gopal | |
dc.contributor.author | Martínez Uña, María Teresa | |
dc.contributor.author | Ingvorsen, Camilla | |
dc.contributor.author | Dias, Ana Rita | |
dc.contributor.author | Relat, Joana | |
dc.contributor.author | Mora, Silvia | |
dc.contributor.author | Hyötyläinen, Tuulia | |
dc.contributor.author | Zorzano, Antonio | |
dc.contributor.author | Oreši, Matej | |
dc.contributor.author | Bjursell, Mikael | |
dc.contributor.author | Bohlooly- Y, Mohammad | |
dc.contributor.author | Lindén, Daniel | |
dc.contributor.author | Vidal- Puig, Antonio | |
dc.date.accessioned | 2021-09-21T12:33:59Z | |
dc.date.available | 2021-09-21T12:33:59Z | |
dc.date.issued | 2021-09 | |
dc.identifier.citation | The FASEB Journal 35(9) : (2021) // Article ID 21752 DOI10.1096/fj.202100262RR | es_ES |
dc.identifier.issn | 0892-6638 | |
dc.identifier.issn | 1530-6860 | |
dc.identifier.uri | http://hdl.handle.net/10810/53118 | |
dc.description.abstract | Aging, obesity, and insulin resistance are associated with low levels of PGC1 alpha and PGC1 beta coactivators and defective mitochondrial function. We studied mice deficient for PGC1 alpha and PGC1 beta [double heterozygous (DH)] to investigate their combined pathogenic contribution. Contrary to our hypothesis, DH mice were leaner, had increased energy dissipation, a pro-thermogenic profile in BAT and WAT, and improved carbohydrate metabolism compared to wild types. WAT showed upregulation of mitochondriogenesis/oxphos machinery upon allelic compensation of PGC1 alpha 4 from the remaining allele. However, DH mice had decreased mitochondrial OXPHOS and biogenesis transcriptomes in mitochondria-rich organs. Despite being metabolically healthy, mitochondrial defects in DH mice impaired muscle fiber remodeling and caused qualitative changes in the hepatic lipidome. Our data evidence first the existence of organ-specific compensatory allostatic mechanisms are robust enough to drive an unexpected phenotype. Second, optimization of adipose tissue bioenergetics is sufficient to maintain a healthy metabolic phenotype despite a broad severe mitochondrial dysfunction in other relevant metabolic organs. Third, the decrease in PGC1s in adipose tissue of obese and diabetic patients is in contrast with the robustness of the compensatory upregulation in the adipose of the DH mice. | es_ES |
dc.description.sponsorship | EC | FP7 | FP7 Health (HEALTH), Grant/Award Number: [HEALTH-F4-2008-223450; RCUK | Medical Research Council (MRC), Grant/Award Number: MC_UU_12012/2 and MC_UU_00014/5; European Commission (EC), Grant/ Award Number: MEIF-CT-2005-023061; Wellcome Trust (Wellcome), Grant/Award Number: 208363/Z/17/Z | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/223450 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | adipose tissue | es_ES |
dc.subject | hepatic lipidome | es_ES |
dc.subject | lipotoxicity | es_ES |
dc.subject | mitochondrial dysfunction | es_ES |
dc.subject | PGC-1alpha | es_ES |
dc.subject | alphaskeletal-musclegene-expression | es_ES |
dc.subject | metabolism | es_ES |
dc.subject | chain | es_ES |
dc.subject | biogenesis | es_ES |
dc.subject | resistance | es_ES |
dc.title | Allostatic hypermetabolic response in PGC1 alpha/beta heterozygote mouse despite mitochondrial defects | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202100262RR | es_ES |
dc.identifier.doi | 10.1096/fj.202100262RR | |
dc.departamentoes | Fisiología | es_ES |
dc.departamentoeu | Fisiologia | es_ES |
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Except where otherwise noted, this item's license is described as © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.