ArticleCell reports2021
FGF21 promotes thermogenic gene expression as an autocrine factor in adipocytes.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 94 citations in OpenAlex.
- Fructose-induced FGF21 secretion does not activate brown adipose tissue in Japanese young men: randomized cross-over and randomized controlled trials.Journal of physiological anthropology · 2024Trial
- Alternative Receptor Signaling for the Selective and Multifaceted Regulation of Human Brown Adipocytes.International journal of molecular sciences · 2026Review
- Follistatin Mitigates Atherosclerosis Through Activation of Arginine Metabolism and Adipose Browning.Cells · 2026Article
- The role of fibroblast growth factor 21 in diabetes and metabolic dysfunction.Molecular biology reports · 2026Review
- Integrative Genomic and Transcriptomic Insights into High-Altitude Adaptation in Changthangi Goats.Applied biochemistry and biotechnology · 2026Article
- Exercise Intensity and Circulating Exerkine Responses: A Narrative Review of Selected Molecules.Biomolecules · 2026Review
- Reexamining Fat: Exploring Diversity, Plasticity, Development, Functional Implication, and Therapeutic Options.International journal of molecular sciences · 2026Review
- Optimizing adipogenic cocktail composition to enhance beige adipogenesis and evaluate thermogenic potential in primary mouse subcutaneous fat cell cultures.International journal of obesity (2005) · 2026Article
- Review
- Cross-Talk Between Signaling and Transcriptional Networks Regulating Thermogenesis-Insights into Canonical and Non-Canonical Regulatory Pathways.International journal of molecular sciences · 2026Review
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- The role of fibroblast growth factors in cell and cancer metabolism.FEBS letters · 2026Review
- Thermogenic adipose tissue in older adults with obesity: a narrative review of mechanisms, brown fat resistance, and the translational relevance of exercise and nutrition.Frontiers in nutrition · 2026Review
- Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity.PeerJ · 2026Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Sex Differences in Ketogenic Diet Response Reveal Gonadal Hormone Interaction With FGF21 in Mice.Journal of the Endocrine Society · 2025Article
- Overexpression of the human heat shock protein B1 alters obesity-related metabolic changes in a sex-dependent manner in a mouse model of metabolic syndrome.Biology of sex differences · 2025Article
- PGC-1α Activation by Polyphenols: A Pathway to Thermogenesis.Molecular nutrition & food research · 2025Review
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- Enhanced paracrine action of FGF21 in stromal cells delays thymic aging.Nature aging · 2025Article
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
The contribution of adipose-derived FGF21 to energy homeostasis is unclear. Here we show that browning of inguinal white adipose tissue (iWAT) by β-adrenergic agonists requires autocrine FGF21 signaling. Adipose-specific deletion of the FGF21 co-receptor β-Klotho renders mice unresponsive to β-adrenergic stimulation. In contrast, mice with liver-specific ablation of FGF21, which eliminates circulating FGF21, remain sensitive to β-adrenergic browning of iWAT. Concordantly, transgenic overexpression of FGF21 in adipocytes promotes browning in a β-Klotho-dependent manner without increasing circulating FGF21. Mechanistically, we show that β-adrenergic stimulation of thermogenic gene expression requires FGF21 in adipocytes to promote phosphorylation of phospholipase C-γ and mobilization of intracellular calcium. Moreover, we find that the β-adrenergic-dependent increase in circulating FGF21 occurs through an indirect mechanism in which fatty acids released by adipocyte lipolysis subsequently activate hepatic PPARα to increase FGF21 expression. These studies identify FGF21 as a cell-autonomous autocrine regulator of adipose tissue function.
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Registered trials
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 Socratic graph.