ArticleNature metabolism2024
Brown fat ATP-citrate lyase links carbohydrate availability to thermogenesis and guards against metabolic stress.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Bioenergetic Materials for Tissue Regeneration: Modulating Metabolism to Promote Cellular Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mutant p53-R280K hijacks SREBP1 to promote fatty acid synthesis and breast cancer progression via FASN.Molecular biology reports · 2026Article
- Gut microbiota as key mediators of animal acclimation to temperature changes: mechanisms and interventions.Applied and environmental microbiology · 2026Review
- Phosphomannomutase 1 restrains adipose thermogenic programming via inosine signaling.Molecular metabolism · 2026Article
- ACLY alleviates cerebral ischemia/reperfusion injury by reducing oxidative stress and enhancing mitochondrial function via histone acetylation.Cell death & disease · 2026Article
- Multi-omics dissection of heat stress reveals CIITA as a central regulator of metabolic thermotolerance in cattle (Bos taurus).Communications biology · 2026Article
- Article
- Functional and metabolomic analyses of brown adipose tissue during cold-deacclimation reveal rapid N-acetylated amino acid adaptations.iScience · 2026Article
- Emerging complexities of phospholipid metabolism in adipose tissue.Molecules and cells · 2026Review
- Adenylosuccinate Synthase 1 Deficiency Improves Energy Metabolism by Promoting Adipose Tissue Re-esterification via Glycerol Kinase Upregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ACLY Safeguards Copper Homeostasis to Sustain Brown Adipose Tissue Thermogenesis and Restrain Diet-Induced Obesity.Research (Washington, D.C.) · 2026Article
- Deciphering Uncoupling Proteins in Cellular Homeostasis and Metabolic Health.International journal of biological sciences · 2026Review
- Fructose uptake by brown adipose tissue is independent of carbohydrate response element-binding protein and does not cause elevatedActa biochimica et biophysica Sinica · 2025Article
- Advanced multifunctional nano-delivery platform focusing on treating diseases related to lipid metabolism via targeted intervention in various lipid metabolic processes.Military Medical Research · 2025Review
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- Optimizing the Bioprocesses of Bacteriocin Production inFoods (Basel, Switzerland) · 2025Article
- Seasonal and Environmental Influences on the Gut Microbiota of South China Tigers (Animals : an open access journal from MDPI · 2025Article
- PPARα regulates ER-lipid droplet protein Calsyntenin-3β to promote ketogenesis in hepatocytes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Adipokines as Cardioprotective Factors: BAT Steps Up to the Plate.Biomedicines · 2025Review
- Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis.Cell reports · 2025Article
Corrections and comments
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Authors and funding
27 authors.
Funding
Abstract
Brown adipose tissue (BAT) engages futile fatty acid synthesis-oxidation cycling, the purpose of which has remained elusive. Here, we show that ATP-citrate lyase (ACLY), which generates acetyl-CoA for fatty acid synthesis, promotes thermogenesis by mitigating metabolic stress. Without ACLY, BAT overloads the tricarboxylic acid cycle, activates the integrated stress response (ISR) and suppresses thermogenesis. ACLY's role in preventing BAT stress becomes critical when mice are weaned onto a carbohydrate-plentiful diet, while removing dietary carbohydrates prevents stress induction in ACLY-deficient BAT. ACLY loss also upregulates fatty acid synthase (Fasn); yet while ISR activation is not caused by impaired fatty acid synthesis per se, deleting Fasn and Acly unlocks an alternative metabolic programme that overcomes tricarboxylic acid cycle overload, prevents ISR activation and rescues thermogenesis. Overall, we uncover a previously unappreciated role for ACLY in mitigating mitochondrial stress that links dietary carbohydrates to uncoupling protein 1-dependent thermogenesis and provides fundamental insight into the fatty acid synthesis-oxidation paradox in BAT.
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Registered trials
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