Hernandez Arturo, Garcia Bibian, Obregon Maria-Jesus
Department of Medicine, Dartmouth Medical School, Borwell Building, Room 720W, Lebanon, New Hampshire 03755, USA.
Endocrinology. 2007 Aug;148(8):3968-76. doi: 10.1210/en.2007-0029. Epub 2007 May 17.
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.
活性甲状腺激素对棕色脂肪组织的分化和功能至关重要。然而，我们观察到在原代培养中分化的棕色前脂肪细胞中，3型脱碘酶（D3）的基础水平和诱导水平都很高，D3是一种使甲状腺激素失活的酶，由印记基因Dio3编码。我们发现，在各种条件下，D3活性和mRNA表达与未分化前体细胞的增殖速率密切相关。此外，前体细胞向脂肪细胞的分化与D3表达水平的降低有关，而在成熟脂肪细胞中仅发现极低水平的D3 mRNA。Dlk1是脂肪细胞分化的抑制剂，也是与Dio3位于同一印记区域的父系表达基因，其表达变化与Dio3平行。相比之下，同样位于同一印记区域的反义基因Dio3os的一个4kb转录本在分化的脂肪细胞中明显上调。我们得出结论，分化中的前脂肪细胞中D3的表达主要与增殖细胞相关，而Dio3os的表达与成熟脂肪细胞相关。我们的结果表明，Dlk1/Dio3印记区域的基因组印记和基因表达可能在脂肪细胞增殖和分化的调节中发挥作用。
