ArticleScientific reports2024
ATF4 expression in thermogenic adipocytes is required for cold-induced thermogenesis in mice via FGF21-independent mechanisms.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Cox10-mediated mitochondrial respiration in brown adipocytes regulates adaptive thermogenesis and systemic metabolism.iScience · 2026Article
- Role of Activating Transcription Factor 4 in Metabolic, Neurologic, and Ocular Diseases.Cells · 2026Review
- Dual Role of Transcription Factors in the Development and Thermogenic Function of Brown Adipose Tissue.International journal of medical sciences · 2026Review
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Regulation of redox homeostasis by ATF4-MTHFD2 axis during white adipose tissue browning.Redox biology · 2025Article
- Cellular Stress Responses and Associated Diseases: A Focus on Heat Shock Proteins.Cell biochemistry and biophysics · 2025Review
- Molecular mechanisms of UCP1-independent thermogenesis: the role of futile cycles in energy dissipation.Journal of physiology and biochemistry · 2025Review
- ATF4 in proximal tubules modulates kidney function and modifies the metabolome.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Aerobic Exercise Activates Fibroblast Growth Factor 21 and Alleviates Cardiac Ischemia/Reperfusion-induced Neuronal Oxidative Stress and Ferroptosis in Paraventricular Nucleus.Molecular neurobiology · 2025Article
- ATF4 Deletion in Brown Adipocytes Attenuates Diet-Induced Insulin Resistance in Male Mice Independently of Weight Gain.Endocrinology · 2025Article
- Emerging Role of GCN1 in Disease and Homeostasis.International journal of molecular sciences · 2024Review
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13 authors at 2 institutions in 1 country.
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Abstract
In brown adipose tissue (BAT), short-term cold exposure induces the activating transcription factor 4 (ATF4), and its downstream target fibroblast growth factor 21 (FGF21). Induction of ATF4 in BAT in response to mitochondrial stress is required for thermoregulation, partially by increasing FGF21 expression. In the present study, we tested the hypothesis that Atf4 and Fgf21 induction in BAT are both required for BAT thermogenesis under physiological stress by generating mice selectively lacking either Atf4 (ATF4 BKO) or Fgf21 (FGF21 BKO) in UCP1-expressing adipocytes. After 3 days of cold exposure, core body temperature was significantly reduced in ad-libitum-fed ATF4 BKO mice, which correlated with Fgf21 downregulation in brown and beige adipocytes, and impaired browning of white adipose tissue. Conversely, despite having reduced browning, FGF21 BKO mice had preserved core body temperature after cold exposure. Mechanistically, ATF4, but not FGF21, regulates amino acid import and metabolism in response to cold, likely contributing to BAT thermogenic capacity under ad libitum-fed conditions. Importantly, under fasting conditions, both ATF4 and FGF21 were required for thermogenesis in cold-exposed mice. Thus, ATF4 regulates BAT thermogenesis under fed conditions likely in a FGF21-independent manner, in part via increased amino acid uptake and metabolism.
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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.