ArticleCell metabolism2022
Cysteine 253 of UCP1 regulates energy expenditure and sex-dependent adipose tissue inflammation.
Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- Emerging roles of mitophagy in liver fibrosis: Implications for therapy.Acta pharmacologica Sinica · 2026Review
- Macrophage-derived itaconate is a negative regulator of adipose tissue thermogenesis.Nature metabolism · 2026Article
- A druggable redox switch on SHP1 controls macrophage inflammation.Nature chemical biology · 2026Article
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- Article
- A small‑molecule HDAC/PDE modulator activates human adipocyte UCP1 and resolves inflammatory signaling.Journal of translational medicine · 2026Article
- A druggable redox switch on SHP1 controls macrophage inflammation.bioRxiv : the preprint server for biology · 2026Article
- From endocrine to immune: therapeutic potential of brown adipose tissue in remodelling the cardiovascular immune microenvironment.Frontiers in immunology · 2026Review
- Deciphering Uncoupling Proteins in Cellular Homeostasis and Metabolic Health.International journal of biological sciences · 2026Review
- Article
- Evaluating the UCP1 expression of brown adipose tissue by quantifying hepatic inflammation using synthetic magnetic resonance imaging: an experimental study with a mouse model.Quantitative imaging in medicine and surgery · 2025Article
- Endocrine regulation of metabolic crosstalk between liver and brown adipose tissue by natural active ingredients.International journal of obesity (2005) · 2025Review
- Branched-chain amino acids contribute to diabetic kidney disease progression via PKM2-mediated podocyte metabolic reprogramming and apoptosis.Nature communications · 2025Article
- New perspectives on polycystic ovary syndrome: hypothalamic-sympathetic-adipose tissue interaction.Journal of ovarian research · 2025Review
- Review
- Oxidative stress in diabetes mellitus and its complications: From pathophysiology to therapeutic strategies.Chinese medical journal · 2025Review
- A Comprehensive Analysis of Sex-Biased Gene Expression in the Aging Human Retina Through a Combination of Single-Cell and Bulk RNA Sequencing.Investigative ophthalmology & visual science · 2025Article
- Adipose tissue-selective ablation of ADAM10 results in divergent metabolic phenotypes following long-term dietary manipulation.Adipocyte · 2024Article
- Fundamentals of redox regulation in biology.Nature reviews. Molecular cell biology · 2024Review
- Sex-Dependent T Cell Dysregulation in Mice with Diet-Induced Obesity.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
Uncoupling protein 1 (UCP1) is a major regulator of brown and beige adipocyte energy expenditure and metabolic homeostasis. However, the widely employed UCP1 loss-of-function model has recently been shown to have a severe deficiency in the entire electron transport chain 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 UCP1 that elevates protein activity upon covalent modification. Here, we examine the physiological importance 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 both males and females but display no measurable effect on fat accumulation in an obesogenic environment. Unexpectedly, we find that a lack of C253 results in adipose tissue redox stress, which drives substantial immune cell infiltration and systemic inflammatory pathology in adipose tissues and liver of male, but not female, mice. Elevation of systemic estrogen reverses this male-specific pathology, providing a basis for protection from inflammation due to loss of UCP1 C253 in females. Together, our results establish the UCP1 C253 activation site as a regulator of acute thermogenesis and sex-dependent tissue inflammation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.