INRA, UR1213 Herbivores, Saint-Genès-Champanelle, France.
J Cell Physiol. 2012 Apr;227(4):1688-700. doi: 10.1002/jcp.22893.
Epidemiological and fetal programming studies point to the role of fetal growth in adult adipose tissue (AT) mass in large mammals. Despite the incidence of fetal AT growth for human health and animal production outcomes, there is still a lack of relevant studies. We determined the cellular and large-scale-molecular features of bovine fetal perirenal AT sampled at 110, 180, 210, and 260 days post-conception (dpc) with the aim of identifying key cellular and molecular events in AT growth. The increase in AT weight from 110 to 260 dpc resulted from an increase in adipocyte volume and particularly adipocyte number that were concomitant with temporal changes in the abundance of 142 proteins revealed by proteomics. At 110 and 180 dpc, we identified proteins such as TCP1, FKBP4, or HSPD1 that may regulate adipocyte precursor proliferation by controlling cell-cycle progression and/or apoptosis or delaying PPARγ-induced differentiation. From 180 dpc, the up-regulation of PPARγ-induced proteins, lipogenic and lipolytic enzymes, and adipokine expression may underpin the differentiation and increase in adipocyte volume. Also from 180 dpc, we unexpectedly observed up-regulations in the β-subunit of ATP synthase, which is normally bypassed in brown AT, as well as in aldehyde dehydrogenases ALDH2 and ALDH9A1, which were predominantly expressed in mouse white AT. These results, together with the observed abundant unilocular adipocytes at 180 and 260 dpc, strongly suggest that fetal bovine perirenal AT has much more in common with white than with brown AT.
流行病学和胎儿编程研究表明,胎儿生长在大型哺乳动物的成年脂肪组织(AT)质量中起作用。尽管胎儿 AT 生长对人类健康和动物生产结果的影响很大,但相关研究仍然缺乏。我们确定了在受精后 110、180、210 和 260 天取样的牛胎儿肾周 AT 的细胞和大规模分子特征,目的是确定 AT 生长中的关键细胞和分子事件。从 110 天到 260 天,AT 重量的增加是由于脂肪细胞体积的增加,特别是脂肪细胞数量的增加,这与蛋白质组学揭示的 142 种蛋白质丰度的时间变化同时发生。在 110 天和 180 天,我们鉴定了 TCP1、FKBP4 或 HSPD1 等蛋白质,它们可能通过控制细胞周期进程和/或细胞凋亡或延迟 PPARγ 诱导的分化来调节脂肪细胞前体的增殖。从 180 天开始,PPARγ 诱导蛋白、脂生成和脂解酶以及脂肪因子表达的上调可能是脂肪细胞体积增加和分化的基础。同样从 180 天开始,我们出人意料地观察到 ATP 合酶β亚基的上调,正常情况下在棕色 AT 中会绕过该亚基,以及醛脱氢酶 ALDH2 和 ALDH9A1 的上调,这两种酶在小鼠白色 AT 中主要表达。这些结果,再加上在 180 天和 260 天观察到丰富的单房脂肪细胞,强烈表明牛胎儿肾周 AT 与白色 AT 而不是棕色 AT 更相似。