Gachkar Sogol, Oelkrug Rebecca, Herrmann Beate, Scanlan Thomas S, Sun Qian, Biebermann Heike, Hoefig Carolin S, Schomburg Lutz, Mittag Jens
Molecular Endocrinology, Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Germany.
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon, USA.
Eur Thyroid J. 2020 Feb;9(2):57-66. doi: 10.1159/000504887. Epub 2019 Dec 20.
Injection of 3-iodothyronamine into experimental animals profoundly affects their metabolism and body temperature. As 3-iodothyronamine is rapidly acetylated in vivo after injection, it was hypothesized that the metabolites N- or O-acetyl-3-iodothyronamines could constitute the active hormones.
Adult male mice were injected once daily with one of the metabolites (5 mg/kg body weight intraperitoneally dissolved in 60% DMSO in PBS) or solvent. Metabolism was monitored by indirect calorimetry, body temperature by infrared thermography, and body composition by nuclear magnetic resonance analysis. Signaling activities in brown fat or liver were assessed by studying target gene transcription by qPCR including uncoupling protein 1 or deiodinase type 1 or 2, and Western blot.
The markers of metabolism, body composition, or temperature tested were similar in the mice injected with solvent and those injected with one of the acetylated 3-iodothyronamines.
In our experimental setup, N- and O-acetyl-3-iodothyronamine do not constitute compounds contributing to the metabolic or temperature effects described for 3-iodothyronamine. The acetylation of 3-iodothyronamine observed in vivo may thus rather serve degradation and elimination purposes.
向实验动物注射3-碘甲腺原氨酸会对其新陈代谢和体温产生深远影响。由于3-碘甲腺原氨酸在注射后于体内迅速乙酰化，因此推测代谢产物N-或O-乙酰-3-碘甲腺原氨酸可能构成活性激素。
成年雄性小鼠每天腹腔注射一次其中一种代谢产物（5毫克/千克体重，溶解于含60%二甲基亚砜的磷酸盐缓冲盐溶液中）或溶剂。通过间接测热法监测新陈代谢，通过红外热成像监测体温，通过核磁共振分析监测身体成分。通过qPCR研究包括解偶联蛋白1或1型或2型脱碘酶在内的靶基因转录，并通过蛋白质免疫印迹法评估棕色脂肪或肝脏中的信号活性。
注射溶剂的小鼠和注射其中一种乙酰化3-碘甲腺原氨酸的小鼠在测试的新陈代谢、身体成分或体温指标方面相似。
在我们的实验设置中，N-和O-乙酰-3-碘甲腺原氨酸并非导致3-碘甲腺原氨酸所描述的代谢或体温效应的化合物。因此，体内观察到的3-碘甲腺原氨酸乙酰化可能主要用于降解和消除。
