The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation.

摘要

The origin of brown adipocytes arising in white adipose tissue (WAT)udafter cold acclimatization is unclear. Here, we demonstrate thatudseveral UCP1-immunoreactive brown adipocytes occurring in WATudafter cold acclimatization have a mixed morphology (paucilocularudadipocytes). These cells also had a mixed mitochondrioma withudclassic “brown” and “white” mitochondria, suggesting intermediateudsteps in the process of direct transformation of white into brownudadipocytes (transdifferentiation). Quantitative electron microscopyuddisclosed that cold exposure (6°C for 10 days) did not induce anudincrease in WAT preadipocytes. 3-adrenoceptor-knockout mice haduda blunted brown adipocyte occurrence upon cold acclimatization.udAdministration of the 3-adrenoceptor agonist CL316,243 induced theudoccurrence of brown adipocytes, with the typical morphologicaludfeatures found after cold acclimatization. In contrast, administrationudof the 1-adrenoceptor agonist xamoterol increased only the numberudof preadipocytes. These findings indicate that transdifferentiationuddepends on 3-adrenoceptor activation, whereas preadipocyte recruitmentudis mediated by 1-adrenoceptor. RT-qPCR experiments disclosedudthat cold exposure induced enhanced expression of the thermogenicudgenes and of genes expressed selectively in brown adiposeudtissue (iBAT) and in both interscapular BAT and WAT. 3-adrenoceptorudsuppression blunted their expression only in WAT. Furthermore,udcold acclimatization induced an increased WAT expression ofudthe gene coding for C/EBP (an antimitotic protein), whereas Ccna1udexpression (related to cell proliferation) was unchanged. Overall, ouruddata strongly suggest that the cold-induced emergence of brownudadipocytes in WAT predominantly reflects 3-adrenoceptor-mediatedudtransdifferentiation.