Lee Debby, Martinez Bridget, Crocker Daniel E, Ortiz Rudy M
Department of Cellular and Molecular Biology, University of California, Merced, California.
Department of Biology, Sonoma State University, Rohnert Park, California.
Physiol Rep. 2017 Feb;5(4). doi: 10.14814/phy2.13114. Epub 2017 Feb 27.
Fasting typically suppresses thyroid hormone (TH)-mediated cellular events and increases sirtuin 1 (SIRT1) activity. THs may regulate metabolism through nongenomic pathways and directly through activation of adenosine monophosphate-activated protein kinase (AMPK). Adult male elephant seals () are active, hypermetabolic, and normothermic during their annual breeding fast, which is characterized by stable TH levels. However, the contribution of TH to maintenance of their fasting metabolism is unknown. To investigate the fasting effects on cellular TH-mediated events and its potential association with SIRT1 and AMPK, we quantified plasma TH levels, mRNA expressions of muscle SIRT1 and TH-associated genes as well as the phosphorylation of AMPK in adult, male northern elephant seals ( = 10/fasting period) over 8 weeks of fasting (early vs. late). Deiodinase type I (DI1) expression increased twofold with fasting duration suggesting that the potential for TH-mediated cellular signaling is increased. AMPK phosphorylation increased 61 ± 21% with fasting suggesting that cellular metabolism is increased. The mRNA expression of the TH transporter, monocarboxylate transporter 10 (MCT10), increased 2.4-fold and the TH receptor (THr-1) decreased 30-fold suggesting that cellular uptake of T is increased, but its subsequent cellular effects such as activation of AMPK are likely nongenomic. The up-regulation of SIRT1 mRNA expression (2.6-fold) likely contributes to the nongenomic activation of AMPK by TH, which may be necessary to maintain the expression of PGC-1 These coordinated changes likely contribute to the up-regulation of mitochondrial metabolism to support the energetic demands associated with prolonged fasting in adult seals.
禁食通常会抑制甲状腺激素(TH)介导的细胞活动,并增加沉默调节蛋白1(SIRT1)的活性。甲状腺激素可能通过非基因组途径以及直接通过激活腺苷酸活化蛋白激酶(AMPK)来调节新陈代谢。成年雄性海象在其一年一度的繁殖禁食期间保持活跃、代谢亢进且体温正常,其特点是甲状腺激素水平稳定。然而,甲状腺激素对维持其禁食代谢的作用尚不清楚。为了研究禁食对细胞甲状腺激素介导事件的影响及其与SIRT1和AMPK的潜在关联,我们在8周的禁食期(早期与晚期)内,对成年雄性北海象(每个禁食期n = 10)的血浆甲状腺激素水平、肌肉SIRT1和甲状腺激素相关基因的mRNA表达以及AMPK的磷酸化进行了量化。I型脱碘酶(DI1)的表达随禁食时间增加了两倍,这表明甲状腺激素介导的细胞信号传导潜力增加。禁食时AMPK磷酸化增加了61±21%,表明细胞代谢增加。甲状腺激素转运体单羧酸转运体10(MCT10)的mRNA表达增加了2.4倍,而甲状腺激素受体(THr-1)减少了30倍,这表明甲状腺激素的细胞摄取增加,但其随后的细胞效应(如AMPK的激活)可能是非基因组的。SIRT1 mRNA表达的上调(2.6倍)可能有助于甲状腺激素对AMPK的非基因组激活,这可能是维持PGC-1表达所必需的。这些协调变化可能有助于线粒体代谢的上调,以支持成年海豹长时间禁食相关的能量需求。