2026-04-17T06:14:20Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1806892025-12-04T21:13:02Zcom_2072_1057col_2072_478781col_2072_478917
RECERCAT author Rodriguez-Cuenca, Sergio author Lelliot, Christopher J author Campbell, Mark author Peddinti, Gopal author Martinez-Uña, Maite author Ingvorsen, Camilla author Rita Dias, Ana author Relat Pardo, Joana author Mora Fayos, Sílvia author Hyötyläinen, Tuulia author Zorzano Olarte, Antonio author Oresic, Matej author Bjursell, Mikael author Bohlooly-Y, Mohammad author Lindén, Daniel author Vidal-Puig, Antonio 2021-10-19T17:08:36Z2021-10-19T17:08:36Z2021-092021-10-19T17:08:36Z Aging, obesity, and insulin resistance are associated with low levels of PGC1α and PGC1β coactivators and defective mitochondrial function. We studied mice deficient for PGC1α and PGC1β [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 PGC1α4 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. (c) The Federation of American Society of Experimental Biology, 2021 info:eu-repo/semantics/openAccess Teixit adipós Mitocondris Malalties Adipose tissues Mitochondria Diseases Allostatic hypermetabolic response in PGC1α/β heterozygote mouse despite mitochondrial defects info:eu-repo/semantics/article info:eu-repo/semantics/submittedVersion