Novel UCP1 knockout models broaden our understanding of mammalian non‐shivering thermogenesis

• Published in: Acta Physiologica 2023-05, Vol.238 (1), p.e13956-n/a
• Main Author: Jastroch, Martin
• Format: Article
• Language: English
• Subjects: Adipose Tissue, Brown; Animals; Mammals; Mice; Mice, Knockout; Mitochondrial Proteins; Thermogenesis; Uncoupling Protein 1
• ISSN: 1748-1708; 1748-1716; 1748-1716
• DOI: 10.1111/apha.13956

In this issue of Acta Physiologica, Warfel et al. advance our knowledge on the physiological significance of brown adipose tissue (BAT) thermogenesis by creating a new uncoupling protein 1 (UCP1)-knockout rat model.1 In mammals, adaptive non-shivering thermogenesis (NST) evolved in BAT to protect high body temperatures of small and newborn species in the cold and to accelerate arousal from hypothermic states, such as torpor and hibernation.2 BAT is specialized for heat production by virtue of rich vascularization, capacity for rapid fatty acid mobilization of multilocular lipid droplets and high mitochondrial density. In BAT mitochondria, a small membrane protein named UCP1 is pivotal for heat production by promoting mitochondrial proton leak.3 The increase of proton leak uncouples mitochondrial respiration from ATP production and accelerates oxidation of energy substrates. UCP1 is almost exclusively expressed in thermogenic adipocytes, which include brown and beige adipocytes, the latter displaying intermediate characteristics between white fat-storing and brown fat-burning cells. BAT fades with age in larger mammals, but residual amounts in adult humans are in the crosshairs as a therapeutic target to combat cardio-metabolic diseases, given BAT's potential to control systemic glucose and lipid metabolism.