Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Theranostics. 2022 Jul 25;12(13):5803-5819. doi: 10.7150/thno.70752. eCollection 2022.
Very preterm infants may require dexamethasone (Dex) for facilitating extubation or treating bronchopulmonary dysplasia. However, Dex may result in disturbance of metabolisms. This study was to investigate the effects of postnatal short course Dex exposure on brown adipose tissue (BAT) in neonatal rats. : Neonatal rats received either three consecutive doses of daily Dex (0.2 mg/kg/day) or saline from postnatal P1 to P3. We investigated the effects of Dex on BAT including thermogenesis, mitochondrial dynamics and autophagy flux. We also compared diurnal temperature variation between preterm infants who received systemic corticosteroid and their treatment-naïve controls. : Postnatal Dex treatment induced growth retardation, BAT whitening, UCP1 downregulation and cold intolerance in neonatal rats. BAT mitochondria were damaged, evident by loss of normal number, structure, and alignment of cristae. Mitochondrial fission-fusion balance was disrupted and skewed toward increased fusion, reflected by increased OPA1 and MFN2 and decreased DRP1, FIS1 and phosphorylated MFF protein levels. Autophagosome synthesis was increased but clearance was inhibited, indicated by accumulation of p62 protein after Dex treatment and no further increase of LC3-II after chloroquine co-treatment. While autophagy modulators, including chloroquine and rapamycin, did not improve UCP1 downregulation and BAT whitening, AMPK activators could partially rescue these damages. We also demonstrated that preterm infants had higher diurnal temperature variation during corticosteroid treatment. : Postnatal short course Dex impaired BAT mitochondrial function and autophagy flux in rat pups. AMPK activators had the potential to rescue the damage.
极早产儿可能需要地塞米松（Dex）来促进拔管或治疗支气管肺发育不良。然而，Dex 可能会导致代谢紊乱。本研究旨在探讨生后短期 Dex 暴露对新生大鼠棕色脂肪组织（BAT）的影响。：新生大鼠从生后第 1 天至第 3 天连续 3 天每天接受 0.2 mg/kg/天的 Dex 或生理盐水处理。我们研究了 Dex 对 BAT 的影响，包括产热、线粒体动力学和自噬通量。我们还比较了接受全身皮质类固醇治疗的早产儿和未治疗对照者之间的日间体温变化。：生后 Dex 处理诱导新生大鼠生长迟缓、BAT 白化、UCP1 下调和不耐寒。BAT 线粒体受损，表现为正常数量、结构和嵴排列丢失。线粒体分裂融合平衡被破坏，向融合增加倾斜，表现为 OPA1 和 MFN2 增加，DRP1、FIS1 和磷酸化 MFF 蛋白水平降低。自噬体合成增加，但清除被抑制，Dex 处理后 p62 蛋白积累，氯喹共处理后 LC3-II 无进一步增加表明这一点。虽然自噬调节剂，包括氯喹和雷帕霉素，不能改善 UCP1 下调和 BAT 白化，但 AMPK 激活剂可以部分挽救这些损伤。我们还表明，早产儿在皮质类固醇治疗期间的日间体温变化更高。：生后短期 Dex 损害了大鼠幼仔的 BAT 线粒体功能和自噬通量。AMPK 激活剂有潜力挽救损伤。
