Ucp1-KO Mouse

Ucp1, short for uncoupling protein 1, is a key effector in thermogenic adipocytes. It dissipates energy in the form of heat by uncoupling the mitochondrial proton gradient from mitochondrial respiration, playing a central role in BAT thermogenesis and systemic energy homeostasis [1]. This process is crucial for mammals to combat hypothermia and metabolic dysregulation [3]. Genetic models, such as gene knockout mice, have been essential in studying Ucp1.

Germline Ucp1 -/- mice have been used to infer Ucp1's role as the sole mediator of adipocyte thermogenesis. However, these mice also have secondary changes in brown adipose tissue. To mitigate such confounding factors, inducible adipocyte-selective Ucp1 disruption mice were constructed. It was found that while germline Ucp1 -/- mice succumb to cold-induced hypothermia, most inducible Ucp1-deleted mice maintain homeothermy in the cold. But co-deletion of Ucp1 and creatine kinase b (Ckb) exacerbates cold intolerance. This suggests that thermogenic adipocytes use non-paralogous protein redundancy through Ucp1 and Ckb for cold-induced energy dissipation [2].

In conclusion, Ucp1 is essential for thermogenesis in adipocytes, regulating energy dissipation and maintaining body temperature. The use of Ucp1 KO and inducible Ucp1-deleted mouse models has revealed not only Ucp1's crucial role in thermogenesis but also its interaction with other proteins like Ckb. These findings contribute to understanding metabolic diseases related to thermogenic dysfunction, offering potential therapeutic targets for conditions such as obesity and type 2 diabetes [1,2].

References:

1. Ikeda, Kenji, Yamada, Tetsuya. 2020. UCP1 Dependent and Independent Thermogenesis in Brown and Beige Adipocytes. In Frontiers in endocrinology, 11, 498. doi:10.3389/fendo.2020.00498. https://pubmed.ncbi.nlm.nih.gov/32849287/

2. Rahbani, Janane F, Bunk, Jakub, Lagarde, Damien, Koza, Robert A, Kazak, Lawrence. 2024. Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB. In Cell metabolism, 36, 526-540.e7. doi:10.1016/j.cmet.2024.01.001. https://pubmed.ncbi.nlm.nih.gov/38272036/

3. Xue, Kaili, Wu, Dongmei, Wang, Yushuang, Wang, Zihao, Qiu, Yifu. 2022. The mitochondrial calcium uniporter engages UCP1 to form a thermoporter that promotes thermogenesis. In Cell metabolism, 34, 1325-1341.e6. doi:10.1016/j.cmet.2022.07.011. https://pubmed.ncbi.nlm.nih.gov/35977541/