Kodde Andrea, Engels Eefje, Oosting Annemarie, van Limpt Kees, van der Beek Eline M, Keijer Jaap
Danone Nutricia Research, Utrecht, Netherlands.
Department of Pediatrics, University Medical Center Groningen - University of Groningen, Groningen, Netherlands.
Front Physiol. 2019 Jul 9;10:836. doi: 10.3389/fphys.2019.00836. eCollection 2019.
White adipose tissue (WAT) distribution and WAT mitochondrial function contribute to total body metabolic health throughout life. Nutritional interventions starting in the postweaning period may impact later life WAT health and function. We therefore assessed changes in mitochondrial density and function markers in WAT depots of young mice. Inguinal (ING), epididymal (EPI) and retroperitoneal (RP) WAT of 21, 42 and 98 days old C57BL/6j mice was collected. Mitochondrial density [citrate synthase (CS), mtDNA] and function [subunits of oxidative phosphorylation complexes (OXPHOS)] markers were analyzed, together with gene expression of browning markers (). mRNA of ING WAT of 21 and 98 old mice was sequenced to further investigate functional changes of the mitochondria and alterations in cell populations. CS levels decreased significantly over time in all depots. ING showed most pronounced changes, including significantly decreased levels of OXPHOS complex I, II, and III subunits and gene expression of (PN21-42 and PN42-98) and (PN42-98). White adipocyte markers were higher at PN98 in ING WAT. Analyses of RNA sequence data showed that the mitochondrial functional profile changed over time from "growth-supporting" mitochondria focused on ATP production (and dissipation), to more steady-state mitochondria with more diverse functions and higher biosynthesis. Mitochondrial density and energy metabolism markers declined in all three depots over time after weaning. This was most pronounced in ING WAT and associated with reduced browning markers, increased whitening and an altered metabolism. In particular the PN21-42 period may provide a time window to study mitochondrial adaptation and effects of nutritional exposures relevant for later life metabolic health.
白色脂肪组织（WAT）的分布及WAT线粒体功能对一生的总体代谢健康都有影响。断奶后开始的营养干预可能会影响晚年WAT的健康和功能。因此，我们评估了幼鼠WAT库中线粒体密度和功能标志物的变化。收集了21日龄、42日龄和98日龄C57BL/6j小鼠的腹股沟（ING）、附睾（EPI）和腹膜后（RP）WAT。分析了线粒体密度[柠檬酸合酶（CS）、线粒体DNA（mtDNA）]和功能[氧化磷酸化复合物（OXPHOS）亚基]标志物，以及褐变标志物的基因表达。对21日龄和98日龄小鼠的ING WAT的mRNA进行测序，以进一步研究线粒体的功能变化和细胞群体的改变。所有脂肪库中CS水平均随时间显著下降。ING的变化最为明显，包括OXPHOS复合物I、II和III亚基水平以及（PN21 - 42和PN42 - 98）和（PN42 - 98）的基因表达显著降低。ING WAT中白色脂肪细胞标志物在PN98时更高。RNA序列数据分析表明，线粒体功能谱随时间从专注于ATP产生（和消耗）的“生长支持型”线粒体，转变为功能更多样化且生物合成更高的更稳定状态的线粒体。断奶后，所有三个脂肪库中线粒体密度和能量代谢标志物均随时间下降。这在ING WAT中最为明显，并与褐变标志物减少、白化增加和代谢改变有关。特别是PN21 - 42期可能提供了一个时间窗口，用于研究线粒体适应性以及与晚年代谢健康相关的营养暴露的影响。
