Varshney Rohan, Das Snehasis, Trahan G Devon, Farriester Jacob W, Mullen Gregory P, Kyere-Davies Gertrude, Presby David M, Houck Julie A, Webb Patricia G, Dzieciatkowska Monika, Jones Kenneth L, Rodeheffer Matthew S, Friedman Jacob E, MacLean Paul S, Rudolph Michael C
Harold Hamm Diabetes Center and Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Pediatrics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
iScience. 2022 Dec 6;26(1):105750. doi: 10.1016/j.isci.2022.105750. eCollection 2023 Jan 20.
Establishing metabolic programming begins during fetal and postnatal development, and early-life lipid exposures play a critical role during neonatal adipogenesis. We define how neonatal consumption of a low omega-6 to -3 fatty acid ratio (n6/n3 FA ratio) establishes FA oxidation in adipocyte precursor cells (APCs) before they become adipocytes. , APCs isolated from mouse pups exposed to the low n6/n3 FA ratio had superior FA oxidation capacity, elevated beige adipocyte mRNAs Ppargc1α, Ucp2, and Runx1, and increased nuclear receptor NR2F2 protein. , APC treatment with NR2F2 ligand-induced beige adipocyte mRNAs and increased mitochondrial potential but not mass. Single-cell RNA-sequencing analysis revealed low n6/n3 FA ratio yielded more mitochondrial-high APCs and linked APC NR2F2 levels with beige adipocyte signatures and FA oxidation. Establishing beige adipogenesis is of clinical relevance, because fat depots with energetically active, smaller, and more numerous adipocytes improve metabolism and delay metabolic dysfunction.
代谢编程始于胎儿期和出生后发育阶段，生命早期的脂质暴露在新生儿脂肪生成过程中起着关键作用。我们确定了新生儿摄入低ω-6与ω-3脂肪酸比例（n6/n3 FA比例）如何在脂肪细胞前体细胞（APC）分化为脂肪细胞之前建立脂肪酸氧化。从暴露于低n6/n3 FA比例的小鼠幼崽中分离出的APC具有更强的脂肪酸氧化能力、米色脂肪细胞相关mRNA（Ppargc1α、Ucp2和Runx1）水平升高以及核受体NR2F2蛋白增加。用NR2F2配体处理APC可诱导米色脂肪细胞相关mRNA表达并增加线粒体电位，但不增加线粒体质量。单细胞RNA测序分析表明，低n6/n3 FA比例产生更多线粒体含量高的APC，并将APC的NR2F2水平与米色脂肪细胞特征和脂肪酸氧化联系起来。建立米色脂肪生成具有临床意义，因为含有能量活跃、体积较小且数量较多的脂肪细胞的脂肪库可改善代谢并延缓代谢功能障碍。
