Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Laboratory of Food and Nutritional Sciences, Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi, Japan.
Front Endocrinol (Lausanne). 2022 Feb 24;13:818064. doi: 10.3389/fendo.2022.818064. eCollection 2022.
Rapid infantile growth (RG) markedly increases the risk of obesity and metabolic disorders in adulthood, particularly among neonates born small. To elucidate the molecular mechanisms by which RG following undernourishment (UN) contributes to the deterioration of adult fat deposition, we developed a UN mouse model using maternal energy restriction, followed by RG achieved by adjustments to 4 pups per litter soon after birth. A high-fat diet (HFD) was fed to weaned pups treated or not (Veh) with tauroursodeoxycholic acid (TU). UN-RG pups showed the deterioration of diet-induced obesity and fat deposition, which was ameliorated by TU. We performed a microarray analysis of epididymal adipose tissue and two gene enrichment analyses (NN-Veh UN-RD-Veh and UN-RG-Veh UN-RG-TU). The results obtained identified 4 common gene ontologies (GO) terms of inflammatory pathways. In addition to the inflammatory characteristics of 4 GO terms, the results of heatmap and principal component analyses of the representative genes from 4 GO terms, genes of interest (GOI; ) selected from the 4 GO terms, and immunohistochemistry of macrophages collectively suggested the critical involvement of inflammation in the regulation of fat deposition in the responses to UN and TU. Therefore, the present results support the 'Developmental Origins of Metaflammation', the last word of which was recently proposed by the concept of metabolic disorders induced by low-grade systemic inflammation.
快速婴儿生长（RG）显著增加了成年后患肥胖和代谢紊乱的风险，尤其是在出生时较小的新生儿中。为了阐明营养不良（UN）后 RG 导致成年脂肪沉积恶化的分子机制，我们使用母体能量限制开发了一种 UN 小鼠模型，随后在出生后不久通过调整每窝 4 只幼崽来实现 RG。断奶幼崽喂食高脂肪饮食（HFD），并接受或不接受牛磺熊脱氧胆酸（TU）处理。UN-RG 幼崽表现出饮食诱导肥胖和脂肪沉积的恶化，而 TU 可改善这种情况。我们对附睾脂肪组织进行了微阵列分析，并进行了两项基因富集分析（NN-Veh UN-RD-Veh 和 UN-RG-Veh UN-RG-TU）。结果确定了 4 个共同的基因本体论（GO）炎症途径术语。除了 4 个 GO 术语的炎症特征外，来自 4 个 GO 术语的代表性基因的热图和主成分分析结果、从 4 个 GO 术语中选择的感兴趣基因（GOI）和巨噬细胞的免疫组织化学结果共同表明炎症在调节对 UN 和 TU 的反应中的脂肪沉积中具有关键作用。因此，目前的结果支持“代谢炎症的发育起源”，这是最近由低水平全身炎症引起的代谢紊乱概念提出的最后一个词。
