美国丹娜-法伯癌症研究所Edward T. Chouchani研究组发现，UCP1的半胱氨酸253调控能量消耗和性别依赖的脂肪组织炎症。2021年12月2日，国际知名学术期刊《细胞—代谢》在线发表了这一成果。

Title: Cysteine 253 of UCP1 regulates energy expenditure and sex-dependent adipose tissue inflammation

Author: Evanna L. Mills, Cathal Harmon, Mark P. Jedrychowski, Haopeng Xiao, Anja V. Gruszczyk, Gary A. Bradshaw, Nhien Tran, Ryan Garrity, Dina Laznik-Bogoslavski, John Szpyt, Hannah Prendeville, Lydia Lynch, Michael P. Murphy, Steven P. Gygi, Bruce M. Spiegelman, Edward T. Chouchani

Issue&Volume: 2021-12-02

Abstract: Uncoupling protein 1 (UCP1) is a major regulator of brown and beige adipocyte energyexpenditure and metabolic homeostasis. However, the widely employed UCP1 loss-of-functionmodel has recently been shown to have a severe deficiency in the entire electron transportchain of thermogenic fat. As such, the role of UCP1 in metabolic regulation in vivo remains unclear. We recently identified cysteine-253 as a regulatory site on UCP1that elevates protein activity upon covalent modification. Here, we examine the physiologicalimportance of this site through the generation of a UCP1 cysteine-253-null (UCP1 C253A)mouse, a precise genetic model for selective disruption of UCP1 in vivo. UCP1 C253A mice exhibit significantly compromised thermogenic responses in bothmales and females but display no measurable effect on fat accumulation in an obesogenicenvironment. Unexpectedly, we find that a lack of C253 results in adipose tissue redoxstress, which drives substantial immune cell infiltration and systemic inflammatorypathology in adipose tissues and liver of male, but not female, mice. Elevation ofsystemic estrogen reverses this male-specific pathology, providing a basis for protectionfrom inflammation due to loss of UCP1 C253 in females. Together, our results establishthe UCP1 C253 activation site as a regulator of acute thermogenesis and sex-dependenttissue inflammation.

DOI: 10.1016/j.cmet.2021.11.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00531-3