Chattergoon Natasha N, Bose Karthikeyan, Louey Samantha, Jonker Sonnet S
Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA.
Physiol Rep. 2025 May;13(10):e70386. doi: 10.14814/phy2.70386.
Fetal circulating lipids are low but rise precipitously following birth. It is unknown how prematurely elevated lipids affect the fetal heart, which primarily uses carbohydrates for energy. Fetal sheep were surgically instrumented and received Intralipid 20® or Lactated Ringer's Solution intravenously. After 8 days, myocardial biopsies were taken, and cardiomyocytes were dispersed. Lipid uptake was assessed by labeled saturated long-chain fatty acids (LCFA) and very long-chain fatty acids (VLCFA) incorporation. Maximal oxygen consumption rates (OCR) were measured. Gene and protein expression levels were measured by quantitative PCR and Western blotting. Intralipid treatment increased LCFA (p < 0.001) and VLCFA (p < 0.001) lipid droplet number, and LCFA (males p = 0.002) and VLCFA (p = 0.018) droplet size. Fetal Intralipid treatment reduced maximal OCR in basal media (p = 0.005). Palmitic acid decreased maximal OCR regardless of fetal treatment or length of in vitro exposure (p = 0.006). Fetal Intralipid upregulated genes included CD36 (p = 0.001), CPT1A (p < 0.001), CPT1B (p < 0.001), VLCAD (p < 0.001), and PDK4 (p < 0.001), with no differences in protein expression. There were no effects on ER stress, apoptosis, or autophagy markers. Extended elevated lipid levels in the fetus increased lipid uptake and may have shifted substrate preference towards lipids, but all lipid exposure depressed fetal cardiac metabolism. Prematurely elevated lipids mature but suppress oxidative metabolism.
胎儿循环中的脂质水平较低，但出生后会急剧上升。目前尚不清楚脂质过早升高如何影响主要利用碳水化合物作为能量来源的胎儿心脏。对胎羊进行手术植入仪器，并静脉注射英脱利匹特20®或乳酸林格氏液。8天后，采集心肌活检样本，并分离出心肌细胞。通过标记的饱和长链脂肪酸（LCFA）和极长链脂肪酸（VLCFA）掺入来评估脂质摄取。测量最大耗氧率（OCR）。通过定量PCR和蛋白质印迹法测量基因和蛋白质表达水平。英脱利匹特治疗增加了LCFA（p < 0.001）和VLCFA（p < 0.001）的脂滴数量，以及LCFA（雄性p = 0.002）和VLCFA（p = 0.018）的脂滴大小。胎儿英脱利匹特治疗降低了基础培养基中的最大OCR（p = 0.005）。无论胎儿治疗情况或体外暴露时间长短，棕榈酸都会降低最大OCR（p = 0.006）。胎儿英脱利匹特上调的基因包括CD36（p = 0.001）、CPT1A（p < 0.001）、CPT1B（p < 0.001）、VLCAD（p < 0.001）和PDK4（p < 0.001），蛋白质表达无差异。对内质网应激、细胞凋亡或自噬标志物无影响。胎儿脂质水平长期升高会增加脂质摄取，并可能使底物偏好转向脂质，但所有脂质暴露都会抑制胎儿心脏代谢。脂质过早升高会使代谢成熟，但会抑制氧化代谢。
