Amorim Mateus R, Foresti Roberta, Benrahla Djamal Eddine, Motterlini Roberto, Branco Luiz G S
Dental School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Temperature (Austin). 2022 Apr 26;9(4):310-317. doi: 10.1080/23328940.2022.2061270. eCollection 2022.
Thermoregulation is critical in health and disease and is tightly controlled to maintain body temperature homeostasis. Carbon monoxide (CO), an endogenous gasotransmitter produced during heme degradation by heme oxygenases, has been suggested to play a role in body core temperature (Tb) regulation. However, a direct involvement of CO in thermoregulation has not been confirmed and its mechanism(s) of action remain largely unknown. In the present study we characterized the effects of systemic delivery of CO by administration of an orally active CO-releasing molecule (CORM-401) on Tb regulation in conscious freely moving rats. Specifically, we evaluated the main thermo effectors in rats treated with CORM-401 by assessing: (i) non-shivering thermogenesis, . the increased metabolism of brown fat measured through oxygen consumption and (ii) the rate of heat loss from the tail through calculations of heat loss index. We found that oral administration of CORM-401 (30 mg/kg) resulted in augmented CO delivery into the blood circulation as evidenced a by significant increase in carbon monoxy hemoglobin levels(COHb). In addition, treatment with CORM-401 increased Tb, which was caused by an elevated non-shivering thermogenesis indicated by increased oxygen consumption without significant changes in the tail heat loss. On the other hand, CORM-401 did not affect blood pressure, but significantly decreased heart rate. In summary, the findings of the present study reveal that increased circulating CO levels lead to a rise in Tb, which could have important implications in the emerging role of CO in the modulation of energetic metabolism.
体温调节在健康和疾病中至关重要，并且受到严格控制以维持体温稳态。一氧化碳（CO）是血红素加氧酶在血红素降解过程中产生的一种内源性气体递质，有人认为它在体核温度（Tb）调节中发挥作用。然而，CO直接参与体温调节尚未得到证实，其作用机制在很大程度上仍然未知。在本研究中，我们通过给予口服活性CO释放分子（CORM-401）来全身递送CO，以此来表征其对清醒自由活动大鼠Tb调节的影响。具体而言，我们通过评估来研究用CORM-401处理的大鼠的主要热效应器：（i）非寒战产热，即通过耗氧量测量褐色脂肪增加的代谢；（ii）通过计算热损失指数来评估尾巴的散热速率。我们发现口服CORM-401（30mg/kg）导致CO向血液循环中的递送增加，这通过碳氧血红蛋白水平（COHb）的显著升高得到证明。此外，用CORM-401处理会使Tb升高，这是由非寒战产热增加引起的，表现为耗氧量增加，而尾巴散热没有显著变化。另一方面，CORM-401不影响血压，但显著降低心率。总之，本研究结果表明，循环中CO水平升高会导致Tb升高，这可能对CO在能量代谢调节中的新作用具有重要意义。
