Gene expression from the imprinted Dio3 locus is associated with cell proliferation of cultured brown adipocytes.
Active thyroid hormones are critical for the differentiation and function of brown adipose tissue. However, we have observed high basal and induced levels of type 3 deiodinase (D3), an enzyme that inactivates thyroid hormones and is coded by the imprinted gene Dio3, in differentiating brown preadipocytes in primary culture. We find that D3 activity and mRNA expression strongly correlate with the rate of proliferation of undifferentiated precursor cells under various conditions. Furthermore, differentiation of precursor cells to adipocytes is associated with decreased levels of D3 expression, and only very low levels of D3 mRNA are found in mature adipocytes. Dlk1, an inhibitor of adipocyte differentiation and a paternally expressed gene located in the same imprinted domain as Dio3, displayed changes in expression that parallel those of Dio3. In contrast, a 4-kb transcript for Dio3os, an antisense gene also located in the same imprinted domain, is markedly up-regulated in differentiated adipocytes. We conclude that D3 expression in differentiating preadipocytes is primarily linked to proliferating cells, whereas Dio3os expression is associated with mature adipocytes. Our results suggest that genomic imprinting and gene expression at the Dlk1/Dio3 imprinted domain may play a role in the regulation of adipocyte proliferation and differentiation.
Hernandez
Arturo
A
Department of Medicine, Dartmouth Medical School, Borwell Building, Room 720W, Lebanon, New Hampshire 03755, USA. arturo.hernandez@dartmouth.edu
Garcia
Bibian
B
Obregon
Maria-Jesus
MJ
D052437:Adipocytes, Brown / Q000166:cytology* / Q000201:enzymology*; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D018392:Genomic Imprinting / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology; D014284:Triiodothyronine / Q000378:metabolism
D001798:Blood Proteins; C512923:Dlk1 protein, rat; D019332:Endothelin-1; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D014284:Triiodothyronine; D016220:Fibroblast Growth Factor 1; D004815:Epidermal Growth Factor; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D008071:Lipoprotein Lipase