Uncoupling Protein 1 Promotes Nile Tilapia Resistance to Acute Cold Stress by Regulating Liver Metabolism

<b>Background</b>: Low temperature stress is a major environmental challenge affecting the growth, metabolism, and survival of many aquaculture species, including Nile tilapia (<i>Oreochromis niloticus</i>). Understanding the molecular mechanisms underlying cold tolerance is therefore essential for improving fish resilience and aquaculture sustainability. <b>Methods</b>: In the present study, an acute cold stress model of Nile tilapia (<i>Oreochromis niloticus</i>) was established and it was found that uncoupling protein 1 (UCP1) was involved in the acute cold stress process of tilapia. <b>Results</b>: The upregulation of UCP1 in the liver under cold stimulation was regulated by stress hormones such as cortisol and adrenaline. UCP1 has a short half-life and is degraded by proteasomes. In tilapia primary hepatocytes, the addition of adrenergic receptor agonists resulted in mitochondrial membrane potential decreasing, while UCP1 siRNA transfection inhibited mitochondrial membrane potential. Biochemical characteristics indicate that UCP1 is a channel protein that mediates proton leakage. In addition, feeding and intraperitoneal injection of mitochondrial uncoupling agent BAM15 can alleviate the low-temperature stress of tilapia. <b>Conclusions</b>: UCP1 helps maintain the metabolic homeostasis of tilapia under acute cold stimulation and provides new insights into the mechanisms of cold resistance as well as potential treatment strategies in fish.