ArticleNature medicine2018
Brown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
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Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 214 citations in OpenAlex.
- Thermogenic Differentiation of Human Adipocyte Precursors in Culture: A Systematic Review.Cells · 2025Pooled it
- Multi-organ proteomic atlas of obesity regression in male mice.Nature metabolism · 2026Article
- Cholesterol-responsive NFE2L1-INSIG1 interaction controls VLDL secretion and metabolic dysfunction-associated steatohepatitis pathogenesis in mice.The Journal of clinical investigation · 2026Article
- Gut microbiota, brown adipose tissue whitening, and obesity: nutritional modulators and metabolic crosstalk.Nutrition & metabolism · 2026Review
- Nrf1 coordinates proteasome activity and autophagy to maintain cardiac proteostasis.Communications biology · 2026Article
- Fasting-mimicking diet induces IFNβ secretion in tumor-associated macrophages via NRF1-mediated ubiquitin-dependent proteolysis of Trex1.British journal of cancer · 2026Article
- CabioRxiv : the preprint server for biology · 2026Article
- Effects of dietary glutamine supplementation on lipid metabolism, fatty acid composition, and taste properties in the longissimus thoracis muscle of feed-restricted yaks.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Review
- Targeting CD44-Hyaluronic Acid Signalling in Obesity Treatment: Insights from Small Molecules and Nanobioconjugates.Nutrition and metabolic insights · 2026Review
- Bidirectional crosstalk between ER stress and lipid metabolism: From proteostasis to tumor adaptation.Cell death discovery · 2025Review
- Purinergic adipocyte-macrophage crosstalk promotes degeneration of thermogenic brown adipose tissue.EMBO reports · 2025Article
- The multifaceted regulation of white adipose tissue browning and their therapeutic potential.Journal of physiology and biochemistry · 2025Review
- Therapeutic potential of traditional Chinese medicine and mechanisms for the treatment of type 2 diabetes mellitus.Chinese medicine · 2025Review
- Thermogenic Adipose ADH5 Counteracts Age-related Metabolic Decline.bioRxiv : the preprint server for biology · 2025Article
- Oxidative Phosphorylation in Uncoupled Mitochondria.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Article
- NRF1 coordinates mitochondrial adaptations to dampen intracellular ROS and inflammatory responses during ischemia reperfusion.Cell death discovery · 2025Article
- Activating the NFE2L1-ubiquitin-proteasome system by DDI2 protects from ferroptosis.Cell death and differentiation · 2025Article
- Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis.Nature communications · 2025Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Adipocytes possess remarkable adaptive capacity to respond to nutrient excess, fasting or cold exposure, and they are thus an important cell type for the maintenance of proper metabolic health. Although the endoplasmic reticulum (ER) is a critical organelle for cellular homeostasis, the mechanisms that mediate adaptation of the ER to metabolic challenges in adipocytes are unclear. Here we show that brown adipose tissue (BAT) thermogenic function requires an adaptive increase in proteasomal activity to secure cellular protein quality control, and we identify the ER-localized transcription factor nuclear factor erythroid 2-like 1 (Nfe2l1, also known as Nrf1) as a critical driver of this process. We show that cold adaptation induces Nrf1 in BAT to increase proteasomal activity and that this is crucial for maintaining ER homeostasis and cellular integrity, specifically when the cells are in a state of high thermogenic activity. In mice, under thermogenic conditions, brown-adipocyte-specific deletion of Nfe2l1 (Nrf1) resulted in ER stress, tissue inflammation, markedly diminished mitochondrial function and whitening of the BAT. In mouse models of both genetic and dietary obesity, stimulation of proteasomal activity by exogenously expressing Nrf1 or by treatment with the proteasome activator PA28α in BAT resulted in improved insulin sensitivity. In conclusion, Nrf1 emerges as a novel guardian of brown adipocyte function, providing increased proteometabolic quality control for adapting to cold or to obesity.
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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.