PDF(Pubmed)
Abstract：
At birth, the fetus experiences a dramatic change in environment that is accompanied by a shift in myocardial fuel preference from lactate and glucose in fetal life to fatty acid oxidation after birth. We hypothesized that fatty acid metabolic machinery would mature during fetal life in preparation for this extreme metabolic transformation at birth. We quantified the pre- (94-day and 135-day gestation, term ∼147 days) and postnatal (5 ± 4 days postnatal) gene expression and protein levels for fatty acid transporters and enzymes in hearts from a precocial species, the sheep. Gene expression of fatty acid translocase (CD36), acyl-CoA synthetase long-chain 1 (ACSL1), carnitine palmitoyltransferase 1 (CPT1), hydroxy-acyl dehydrogenase (HADH), acetyl-CoA acetyltransferase (ACAT1), isocitrate dehydrogenase (IDH), and glycerol phosphate acyltransferase (GPAT) progressively increased through the perinatal period, whereas several genes [fatty acid transport protein 6 (FATP6), acyl-CoA synthetase long chain 3 (ACSL3), long-chain acyl-CoA dehydrogenase (LCAD), very long-chain acyl-CoA dehydrogenase (VLCAD), pyruvate dehydrogenase kinase (PDK4), phosphatidic acid phosphatase (PAP), and diacylglycerol acyltransferase (DGAT)] were stable in fetal hearts and had high expression after birth. Protein expression of CD36 and ACSL1 progressively increased throughout the perinatal period, whereas protein expression of carnitine palmitoyltransferase 1a (fetal isoform) (CPT1a) decreased and carnitine palmitoyltransferase 1b (adult isoform) (CPT1b) remained constitutively expressed. Using fluorescent-tagged long-chain fatty acids (BODIPY-C12), we demonstrated that fetal (125 ± 1 days gestation) cardiomyocytes produce 59% larger lipid droplets (P < 0.05) compared with newborn (8 ± 1 day) cardiomyocytes. These results provide novel insights into the perinatal maturation of cardiac fatty acid metabolism in a precocial species.NEW & NOTEWORTHY This study characterized the previously unknown expression patterns of genes that regulate the metabolism of free fatty acids in the perinatal sheep myocardium. This study shows that the prenatal myocardium prepares for the dramatic switch from carbohydrate metabolism to near complete reliance on free fatty acids postnatally. Fetal and neonatal cardiomyocytes also demonstrate differing lipid storage mechanisms where fetal cardiomyocytes form larger lipid droplets compared with newborn cardiomyocytes.
摘要：
出生时,胎儿经历了环境的急剧变化，伴随着心肌燃料的偏好从胎儿生命中的乳酸和葡萄糖转变为出生后的脂肪酸氧化。我们假设脂肪酸代谢机制会在胎儿时期成熟，为出生时的这种极端代谢转化做准备。我们量化了妊娠前(94天和135天，长期〜147天）和出生后（出生后5±4天）来自早熟物种的心脏中脂肪酸转运蛋白和酶的基因表达和蛋白质水平，羊。CD36、ACSL1、CPT1、HADH、ACAT1，IDH和GPAT在围产期逐渐增加，而几个基因FATP6，ACSL3，LCAD，VLCAD,PDK4、PAP和DGAT在胎儿心脏中稳定，出生后高表达。CD36和ACSL1的蛋白表达在整个围产期逐渐增加，而CPT1a下降，CPT1b保持组成型表达。使用荧光标记的长链脂肪酸（BODIPYC12），我们证实,与新生(8±1天)心肌细胞相比,胎儿(妊娠125±1天)心肌细胞产生的脂滴增大了59%(p<0.05).这些结果为早熟物种中心脏脂肪酸代谢的围产期成熟提供了新的见解。
