Ucp1-KO Mouse

Ucp1, short for uncoupling protein 1, is a key effector in thermogenic adipocytes. It plays a central role in the process of dissipating energy in the form of heat by uncoupling the mitochondrial proton gradient from mitochondrial respiration, a process crucial for adaptive thermogenesis. This thermogenic capacity of Ucp1-expressing adipocytes has potential therapeutic implications for metabolic diseases like obesity and type 2 diabetes [1,2].

Germline Ucp1-/-mice have been used to study its function. The conventional view that Ucp1 is the sole mediator of adipocyte thermogenesis was mainly inferred from the attenuation of thermogenic output in these mice. However, such mice have secondary changes within brown adipose tissue. To mitigate these 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 inducible co-deletion of Ucp1 and creatine kinase b (Ckb) exacerbates cold intolerance, suggesting non-paralogous protein redundancy through Ucp1 and Ckb in promoting cold-induced energy dissipation [3].

In conclusion, Ucp1 is essential for the thermogenic function of brown and beige adipocytes. The study of Ucp1 using gene knockout mouse models, especially germline Ucp1-/-and inducible adipocyte-selective Ucp1-deleted mice, has provided insights into its role in thermogenesis and energy homeostasis. This understanding is valuable for exploring potential treatments for metabolic disorders such as obesity and type 2 diabetes [1,2,3].

References:

1. Chouchani, Edward T, Kazak, Lawrence, Spiegelman, Bruce M. 2018. New Advances in Adaptive Thermogenesis: UCP1 and Beyond. In Cell metabolism, 29, 27-37. doi:10.1016/j.cmet.2018.11.002. https://pubmed.ncbi.nlm.nih.gov/30503034/

2. 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/

3. 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/