Genetic Background Strongly Influences the Impact of Carrying the Thr92Ala-DIO2 Polymorphism in the Male Mouse

Página do item simplificado
dc.contributor.authorGabriel De Almeida G.
dc.contributor.authorBolin A.P.
dc.contributor.authorBatistuzzo A.
dc.contributor.authorFonseca T.L.
dc.contributor.authorRibeiro M.O.
dc.contributor.authorBianco A.C.
dc.date.accessioned2024-07-01T06:10:23Z
dc.date.available2024-07-01T06:10:23Z
dc.date.issued2024
dc.description.abstract© 2024 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.About half of the world population carries at least one allele of the Ala92-DIO2, which slows down the activity of the type 2 deiodinase (D2), the enzyme that activates T4 to T3. Carrying the Ala92-DIO2 allele has been associated with increased body mass index and insulin resistance, but this has not been reproduced in all populations. To test if the genetic background affects the impact of this polymorphism, here we studied the genetically distant C57Bl/6J (B6) and FVB/N (FVB) mice carrying the Ala92-Dio2 allele as compared to control mice carrying the Thr92-Dio2 allele. Whereas B6-Ala92-Dio2 and B6-Thr92-Dio2 mice - fed chow or high-fat diet - behaved metabolically similar in studies using indirect calorimetry, glucose- and insulin tolerance tests, and measuring white adipose tissue (WAT) weight and liver steatosis, major differences were observed between FVB-Ala92-Dio2 and FVB-Thr92-Dio2 mice: carrying the Ala92-Dio2 allele (on a chow diet) resulted in hypercholesterolemia, smaller WAT pads, hepatomegaly, steatosis, and transcriptome changes in the interscapular brown adipose tissue (iBAT) typical of ER stress and apoptosis. Acclimatization at thermoneutrality (30 °C) eliminated most of the metabolic phenotype, indicating that impaired adaptive (BAT) thermogenesis can be involved. In conclusion, the metabolic impact of carrying the Ala92-Dio2 allele depends greatly on the genetic background of the mouse, varying from no phenotype in B6 mice to a major phenotype in FVB mice. These results will help the planning of future clinical trials studying the Thr92Ala-DIO2 polymorphism and may explain why some clinical studies performed in different populations across the globe have obtained inconsistent results.
dc.description.issuenumber7
dc.description.volume165
dc.identifier.doi10.1210/endocr/bqae064
dc.identifier.issnNone
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/38796
dc.relation.ispartofEndocrinology (United States)
dc.rightsAcesso Restrito
dc.subject.otherlanguagedeiodinases
dc.subject.otherlanguagelipids
dc.subject.otherlanguagesteatosis
dc.subject.otherlanguagethyroid hormone
dc.titleGenetic Background Strongly Influences the Impact of Carrying the Thr92Ala-DIO2 Polymorphism in the Male Mouse
dc.typeArtigo
local.scopus.citations1
local.scopus.eid2-s2.0-85196211659
local.scopus.subjectAdipose Tissue, Brown
local.scopus.subjectAdipose Tissue, White
local.scopus.subjectAnimals
local.scopus.subjectDiet, High-Fat
local.scopus.subjectFatty Liver
local.scopus.subjectGenetic Background
local.scopus.subjectInsulin Resistance
local.scopus.subjectIodide Peroxidase
local.scopus.subjectIodothyronine Deiodinase Type II
local.scopus.subjectMale
local.scopus.subjectMice
local.scopus.subjectMice, Inbred C57BL
local.scopus.subjectPolymorphism, Genetic
local.scopus.updated2025-04-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85196211659&origin=inward
Arquivos
Coleções
Artigos de periódico