ArticleThe Journal of biological chemistry2014
Fibroblast growth factor 21 is regulated by the IRE1α-XBP1 branch of the unfolded protein response and counteracts endoplasmic reticulum stress-induced hepatic steatosis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.
- Effect of SGLT2 Inhibitors on Type 2 Diabetes Mellitus With Non-Alcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials.Frontiers in endocrinology · 2021Pooled it
- Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study.Diabetologia · 2018Trial
- FGF21 induced by endoplasmic reticulum stress maintains medullary thymic epithelial cell function and central immune tolerance.Science advances · 2026Article
- Influence of Fibroblast Growth Factor 21 on Delayed Glycemic Improvement Following Acute Exercise in Type 2 Diabetes Mellitus.Diabetes & metabolism journal · 2026Article
- ATP6V1B2 alleviates hepatic steatosis by promoting lysosomal acidification in hepatocytes.Cell death discovery · 2026Article
- Osthole Activates FGF21 Expression by Mediating Activation of ATF4 in Human Hepatocyte HepG2 Cells.International journal of molecular sciences · 2026Article
- Hepatokines and polycystic ovary syndrome: investigating the connection between the hepato-ovarian axis and disorders in glycolipid metabolism in PCOS: a narrative review.Frontiers in endocrinology · 2026Review
- Functions of FGF21 and its role in cardiac hypertrophy.Journal of advanced research · 2026Review
- Fibroblast Growth Factor 21: Mechanisms, Therapeutic Potential, and Clinical Translation in Metabolic Dysfunction.Drug design, development and therapy · 2026Review
- Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer.Pharmacological reviews · 2025Review
- Pharmacotherapy in metabolic-dysfunction-associated steatotic liver disease: an updated review of the past, present and a promising future.Diabetology international · 2025Article
- Associations among serum FGF21 levels, inflammation, and metabolic dysfunction-associated steatotic liver disease: mediation analyses in a Chinese community-based population.Endocrine connections · 2025Article
- Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications.MedComm · 2025Review
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- Treating metabolic dysfunction-associated steatohepatitis: The fat-trimming FGF21 approach.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.Research (Washington, D.C.) · 2025Review
- Research progress on the role of FGF21 in insulin resistance.Frontiers in endocrinology · 2025Review
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- Cancer-associated fibroblasts maintain critical pancreatic cancer cell lipid homeostasis in the tumor microenvironment.Cell reports · 2024Article
- Hepatocyte-specific GDF15 overexpression improves high-fat diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction.Scientific reports · 2024Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress activates the adaptive unfolded protein response (UPR) and represents a critical mechanism that underlies metabolic dysfunctions. Fibroblast growth factor 21 (FGF21), a hormone that is predominantly secreted by the liver, exerts a broad range of effects upon the metabolism of carbohydrates and lipids. Although increased circulating levels of FGF21 have been documented in animal models and human subjects with obesity and nonalcoholic fatty liver disease, the functional interconnections between metabolic ER stress and FGF21 are incompletely understood. Here, we report that increased ER stress along with the simultaneous elevation of FGF21 expression were associated with the occurrence of nonalcoholic fatty liver disease both in diet-induced obese mice and human patients. Intraperitoneal administration of the ER stressor tunicamycin in mice resulted in hepatic steatosis, accompanied by activation of the three canonical UPR branches and increased the expression of FGF21. Furthermore, the IRE1α-XBP1 pathway of the UPR could directly activate the transcriptional expression of Fgf21. Administration of recombinant FGF21 in mice alleviated tunicamycin-induced liver steatosis, in parallel with reduced eIF2α-ATF4-CHOP signaling. Taken together, these results suggest that FGF21 is an integral physiological component of the cellular UPR program, which exerts beneficial feedback effects upon lipid metabolism through counteracting ER stress.
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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.