Thyroid hormone increases fatty acid use in fetal ovine cardiac myocytes.
Thyroid hormone increases fatty acid use in fetal ovine cardiac myocytes.
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DOI：
10.14814/phy2.15865
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发表时间：
2023-11
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
--
作者：
分娩时，心脏代谢底物偏好从碳水化合物转变为脂肪酸。我们假设甲状腺激素(T3)和棕榈酸(PA)能刺激胎儿心肌细胞的氧化代谢能力。以1.5 NM为靶点，将T3注入胎羊体内。用BODIPY标记的脂肪酸评估分散的心肌细胞的脂质摄取和液滴形成。用聚合酶链式反应检测心肌组织的表达水平。将幼稚胎儿的心肌细胞暴露于T3和PA，并用海马生物分析仪测量耗氧量。子宫内暴露于升高的T3的心肌细胞(130天胎龄)比输注车辆的胎儿细胞积累的长链脂肪酸液滴多42%。在子宫内，T3增加了心肌细胞CD36、CPT1a、CPT1B、LCAD、VLCAD、HADH、IDH、PDK4和Caspase9的基因表达水平。在体外，在没有脂肪酸和PA作为细胞能量急性供应(30 分钟)的情况下，T3增加了培养心肌细胞的最大耗氧率。长期暴露于PA(24和48 h)可抑制培养心肌细胞中T3水平升高所刺激的氧耗率增加。T3有助于胎儿心肌细胞的代谢成熟。然而，胎儿心肌细胞长期暴露于PA可能会削弱氧化能力。
Cardiac metabolic substrate preference shifts at parturition from carbohydrates to fatty acids. We hypothesized that thyroid hormone (T3) and palmitic acid (PA) stimulate fetal cardiomyocyte oxidative metabolism capacity. T3 was infused into fetal sheep to a target of 1.5 nM. Dispersed cardiomyocytes were assessed for lipid uptake and droplet formation with BODIPY‐labeled fatty acids. Myocardial expression levels were assessed PCR. Cardiomyocytes from naïve fetuses were exposed to T3 and PA, and oxygen consumption was measured with the Seahorse Bioanalyzer. Cardiomyocytes (130‐day gestational age) exposed to elevated T3 in utero accumulated 42% more long‐chain fatty acid droplets than did cells from vehicle‐infused fetuses. In utero T3 increased myocardial mRNA levels of CD36, CPT1A, CPT1B, LCAD, VLCAD, HADH, IDH, PDK4, and caspase 9. In vitro exposure to T3 increased maximal oxygen consumption rate in cultured cardiomyocytes in the absence of fatty acids, and when PA was provided as an acute (30 min) supply of cellular energy. Longer‐term exposure (24 and 48 h) to PA abrogated increased oxygen consumption rates stimulated by elevated levels of T3 in cultured cardiomyocytes. T3 contributes to metabolic maturation of fetal cardiomyocytes. Prolonged exposure of fetal cardiomyocytes to PA, however, may impair oxidative capacity.
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影响因子：
11.1
作者：
Krahmer, Natalie;Farese, Robert V., Jr.;Walther, Tobias C.
通讯作者：
Walther, Tobias C.
影响因子：
37.8
作者：
Goldberg IJ;Reue K;Abumrad NA;Bickel PE;Cohen S;Fisher EA;Galis ZS;Granneman JG;Lewandowski ED;Murphy R;Olive M;Schaffer JE;Schwartz-Longacre L;Shulman GI;Walther TC;Chen J
通讯作者：
Chen J
影响因子：
5
作者：
O'Donnell, J. Michael;Fields, Aaron D.;Lewandowski, E. Douglas
通讯作者：
Lewandowski, E. Douglas
影响因子：
4.8
作者：
Chattergoon, Natasha N.;Giraud, George D.;Thornburg, Kent L.
通讯作者：
Thornburg, Kent L.
影响因子：
5.5
作者：
Drake, Rachel R.;Louey, Samantha;Thornburg, Kent L.
通讯作者：
Thornburg, Kent L.