The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic

Fibroblast growth factor (FGF)-21 based therapies: A magic bullet for nonalcoholic fatty liver disease (NAFLD)?

(2020) Michael Ritchie et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Endogenous FGF21-signaling controls paradoxical obesity resistance of UCP1-deficient mice

(2020) Susanne Keipert et al.   Nature Communications

Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation

(2019) Yong Pan et al.   JOURNAL OF CLINICAL INVESTIGATION

Exercise Alleviates Obesity-Induced Metabolic Dysfunction via Enhancing FGF21 Sensitivity in Adipose Tissues

(2019) Leiluo Geng et al.   Cell Reports

The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform

(2019) Karin Hultman et al.   JOURNAL OF COMPARATIVE NEUROLOGY

Circulating FGF21 Levels in Human Health and Metabolic Disease

(2019) Michaela Keuper et al.   EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES

Exercise ameliorates the FGF21–adiponectin axis impairment in diet-induced obese mice

(2019) Wenqi Yang et al.   Endocrine Connections

140-LB: NGM313, a Novel Activator of b-Klotho/FGFR1c, Improves Insulin Resistance and Reduces Hepatic Fat in Obese, Nondiabetic Subjects

(2019) ALEX DEPAOLI et al.   DIABETES

Going Back to the Biology of FGF21: New Insights

(2019) Jo E. Lewis et al.   TRENDS IN ENDOCRINOLOGY AND METABOLISM

Improved FGF21 Sensitivity and Restored FGF21 Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats After Duodenal-Jejunal Bypass and Sleeve Gastrectomy

(2019) Qiaoran Liu et al.   Frontiers in Endocrinology

Paracrine-endocrine FGF chimeras as potent therapeutics for metabolic diseases

(2019) Longwei Zhao et al.   EBioMedicine

Increased Expression of FGF‐21 Negatively Affects Bone Homeostasis in Dystrophin/Utrophin Double Knockout Mice

(2019) Hongshuai Li et al.   JOURNAL OF BONE AND MINERAL RESEARCH

Whole-body and adipose tissue-specific mechanisms underlying the metabolic effects of fibroblast growth factor 21 in the Siberian hamster

(2019) Jo E. Lewis et al.   Molecular Metabolism

A long-acting FGF21 alleviates hepatic steatosis and inflammation in a mouse model of non-alcoholic steatohepatitis partly through an FGF21-adiponectin-IL17A pathway

(2018) Lichen Bao et al.   BRITISH JOURNAL OF PHARMACOLOGY

A 2A Receptor Activation Attenuates Hypertensive Cardiac Remodeling via Promoting Brown Adipose Tissue-Derived FGF21

(2018) Cheng-Chao Ruan et al.   Cell Metabolism

FGF Family: From Drug Development to Clinical Application

(2018) Qi Hui et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys

(2018) Birgitte Andersen et al.   INTERNATIONAL JOURNAL OF OBESITY

A biparatopic agonistic antibody that mimics fibroblast growth factor 21 ligand activity

(2018) Sally Yu Shi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

BMS-986036, a PEGylated fibroblast growth factor 21 analogue, reduces fibrosis and Pro-C3 in a mouse model of non-alcoholic steatohepatitis

(2018) Y. Luo et al.   JOURNAL OF HEPATOLOGY

Effects of a PEGylated fibroblast growth factor 21 variant on steatosis, inflammation, and fibrosis in a mouse model of nonalcoholic steatohepatitis

(2018) B. Zinker et al.   JOURNAL OF HEPATOLOGY

Effects of central FGF21 infusion on the hypothalamus–pituitary–thyroid axis and energy metabolism in rats

(2018) Umit Yilmaz et al.   Journal of Physiological Sciences

Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease

(2018) Mohammad Zarei et al.   Molecular Metabolism

Agonistic β-Klotho antibody mimics fibroblast growth factor 21 (FGF21) functions

(2018) Xiaoshan Min et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structures of β-klotho reveal a ‘zip code’-like mechanism for endocrine FGF signalling

(2018) Sangwon Lee et al.   NATURE

Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial

(2018) Arun Sanyal et al.   LANCET

Pegbelfermin (BMS-986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study

(2018) Edgar D. Charles et al.   Obesity

Fibroblast activation protein is dispensable for control of glucose homeostasis and body weight in mice

(2018) Brandon L. Panaro et al.   Molecular Metabolism

A Novel Fc-FGF21 With Improved Resistance to Proteolysis, Increased Affinity Toward β-Klotho, and Enhanced Efficacy in Mice and Cynomolgus Monkeys

(2017) Shanaka Stanislaus et al.   ENDOCRINOLOGY

FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans

(2017) Ricardo J Samms et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

FGF21 mimetic antibody stimulates UCP1-independent brown fat thermogenesis via FGFR1/βKlotho complex in non-adipocytes

(2017) Mark Z. Chen et al.   Molecular Metabolism

FAP finds FGF21 easy to digest

(2016) M. P. Gillum et al.   BIOCHEMICAL JOURNAL

FGF21 Regulates Sweet and Alcohol Preference

(2016) Saswata Talukdar et al.   Cell Metabolism

A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects

(2016) Saswata Talukdar et al.   Cell Metabolism

FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues

(2016) Christian Schlein et al.   Cell Metabolism

FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver

(2016) Stephanie von Holstein-Rathlou et al.   Cell Metabolism

FGF21 Improves the Adipocyte Dysfunction Related to Seipin Deficiency

(2016) Lucile Dollet et al.   DIABETES

Overexpression of β-Klotho in Adipose Tissue Sensitizes Male Mice to Endogenous FGF21 and Provides Protection From Diet-Induced Obesity

(2016) Ricardo J. Samms et al.   ENDOCRINOLOGY

Fibroblast growth factor 21 improves hepatic insulin sensitivity by inhibiting mammalian target of rapamycin complex 1 in mice

(2016) Qi Gong et al.   HEPATOLOGY

Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21

(2016) Diana Ronai Dunshee et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Fibroblast growth factor-21 restores insulin sensitivity but induces aberrant bone microstructure in obese insulin-resistant rats

(2016) Narattaphol Charoenphandhu et al.   JOURNAL OF BONE AND MINERAL METABOLISM

PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates

(2016) W. Clayton Thompson et al.   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-β/smad2/3 and NF-κB signaling pathways

(2016) Pengfei Xu et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes

(2016) Annabel Y. Minard et al.   Cell Reports

Fibroblast activation protein (FAP) as a novel metabolic target

(2016) Miguel Angel Sánchez-Garrido et al.   Molecular Metabolism

Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk

(2016) Leigang Jin et al.   Diabetes & Metabolism Journal

Human FGF-21 Is a Substrate of Fibroblast Activation Protein

(2016) Andrew L. Coppage et al.   PLoS One

FGF21 attenuates pathological myocardial remodeling following myocardial infarction through the adiponectin-dependent mechanism

(2015) Yusuke Joki et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Circulating FGF21 proteolytic processing mediated by fibroblast activation protein

(2015) E. Y. Zhen et al.   BIOCHEMICAL JOURNAL

A Liver-Bone Endocrine Relay by IGFBP1 Promotes Osteoclastogenesis and Mediates FGF21-Induced Bone Resorption

(2015) Xunde Wang et al.   Cell Metabolism

Pharmacologic Effects of FGF21 Are Independent of the “Browning” of White Adipose Tissue

(2015) Murielle M. Véniant et al.   Cell Metabolism

Fibroblast Growth Factor 21 Prevents Atherosclerosis by Suppression of Hepatic Sterol Regulatory Element-Binding Protein-2 and Induction of Adiponectin in Mice

(2015) Z. Lin et al.   CIRCULATION

Fibroblast growth factor 21 protects the heart from apoptosis in a diabetic mouse model via extracellular signal-regulated kinase 1/2-dependent signalling pathway

(2015) Chi Zhang et al.   DIABETOLOGIA

Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice

(2015) Nicholas Douris et al.   ENDOCRINOLOGY

FGF21 deletion exacerbates diabetic cardiomyopathy by aggravating cardiac lipid accumulation

(2015) Xiaoqing Yan et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

FGF21 and the late adaptive response to starvation in humans

(2015) Pouneh K. Fazeli et al.   JOURNAL OF CLINICAL INVESTIGATION

Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23

(2015) Chiara Degirolamo et al.   NATURE REVIEWS DRUG DISCOVERY

Expression Atlas update—an integrated database of gene and protein expression in humans, animals and plants

(2015) Robert Petryszak et al.   NUCLEIC ACIDS RESEARCH

FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1

(2015) Michelle M. Kwon et al.   Cell Reports

Discrete Aspects of FGF21 In Vivo Pharmacology Do Not Require UCP1

(2015) Ricardo J. Samms et al.   Cell Reports

FGF21 and Cardiac Physiopathology

(2015) Anna Planavila et al.   Frontiers in Endocrinology

Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex

(2015) Ganesh Kolumam et al.   EBioMedicine

Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue

(2015) Mohamed Asrih et al.   PLoS One

Fibroblast growth factor 21 protects the heart from oxidative stress

(2014) Anna Planavila et al.   CARDIOVASCULAR RESEARCH

FGF21 Acts Centrally to Induce Sympathetic Nerve Activity, Energy Expenditure, and Weight Loss

(2014) Bryn M. Owen et al.   Cell Metabolism

FGF21 Maintains Glucose Homeostasis by Mediating the Cross Talk Between Liver and Brain During Prolonged Fasting

(2014) Q. Liang et al.   DIABETES

Circulating FGF21 Is Liver Derived and Enhances Glucose Uptake During Refeeding and Overfeeding

(2014) K. R. Markan et al.   DIABETES

Fibroblast growth factor 21 participates in adaptation to endoplasmic reticulum stress and attenuates obesity-induced hepatic metabolic stress

(2014) Seong Hun Kim et al.   DIABETOLOGIA

Fibroblast Growth Factor 21 Limits Lipotoxicity by Promoting Hepatic Fatty Acid Activation in Mice on Methionine and Choline-Deficient Diets

(2014) Ffolliott M. Fisher et al.   GASTROENTEROLOGY

Fibroblast growth factor 21 protects against acetaminophen-induced hepatotoxicity by potentiating peroxisome proliferator-activated receptor coactivator protein-1α-mediated antioxidant capacity in mice

(2014) Dewei Ye et al.   HEPATOLOGY

Opposite alterations in FGF21 and FGF19 levels and disturbed expression of the receptor machinery for endocrine FGFs in obese patients

(2014) J M Gallego-Escuredo et al.   INTERNATIONAL JOURNAL OF OBESITY

Fibroblast growth factor 21 is induced upon cardiac stress and alters cardiac lipid homeostasis

(2014) Manoja K. Brahma et al.   JOURNAL OF LIPID RESEARCH

MicroRNA 34a Inhibits Beige and Brown Fat Formation in Obesity in Part by Suppressing Adipocyte Fibroblast Growth Factor 21 Signaling and SIRT1 Function

(2014) T. Fu et al.   MOLECULAR AND CELLULAR BIOLOGY

A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity

(2014) Daniel A Bachovchin et al.   Nature Chemical Biology

Understanding fibroblast activation protein (FAP): Substrates, activities, expression and targeting for cancer therapy

(2014) Elizabeth J. Hamson et al.   Proteomics Clinical Applications

Adiponectin Mediates the Metabolic Effects of FGF21 on Glucose Homeostasis and Insulin Sensitivity in Mice

(2013) Zhuofeng Lin et al.   Cell Metabolism

An FGF21-Adiponectin-Ceramide Axis Controls Energy Expenditure and Insulin Action in Mice

(2013) William L. Holland et al.   Cell Metabolism

The Effects of LY2405319, an FGF21 Analog, in Obese Human Subjects with Type 2 Diabetes

(2013) Gregory Gaich et al.   Cell Metabolism

High Glucose Represses  -Klotho Expression and Impairs Fibroblast Growth Factor 21 Action in Mouse Pancreatic Islets: Involvement of Peroxisome Proliferator-Activated Receptor   Signaling

(2013) W. Y. So et al.   DIABETES

Pegylated Fgf21 rapidly normalizes insulin-stimulated glucose utilization in diet-induced insulin resistant mice

(2013) Raul C. Camacho et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Influence of growth hormone on circulating fibroblast growth factor 21 levels in humans

(2013) J. Lundberg et al.   JOURNAL OF INTERNAL MEDICINE

FGF21 regulates metabolism and circadian behavior by acting on the nervous system

(2013) Angie L Bookout et al.   NATURE MEDICINE

Rational Design of a Fibroblast Growth Factor 21-Based Clinical Candidate, LY2405319

(2013) Alexei Kharitonenkov et al.   PLoS One

Fibroblast growth factor 21 protects against cardiac hypertrophy in mice

(2013) A. Planavila et al.   Nature Communications

Fibroblast Growth Factor-21 Regulates PPARγ Activity and the Antidiabetic Actions of Thiazolidinediones

(2012) Paul A. Dutchak et al.   CELL

Selective Insulin and Leptin Resistance in Metabolic Disorders

(2012) A. Christine Könner et al.   Cell Metabolism

βKlotho Is Required for Fibroblast Growth Factor 21 Effects on Growth and Metabolism

(2012) Xunshan Ding et al.   Cell Metabolism

TNF-α Represses β-Klotho Expression and Impairs FGF21 Action in Adipose Cells: Involvement of JNK1 in the FGF21 Pathway

(2012) Julieta Díaz-Delfín et al.   ENDOCRINOLOGY

FGF21 Is Increased by Inflammatory Stimuli and Protects Leptin-Deficientob/obMice from the Toxicity of Sepsis

(2012) Kenneth R. Feingold et al.   ENDOCRINOLOGY

FGF21 regulates PGC-1  and browning of white adipose tissues in adaptive thermogenesis

(2012) f. M. Fisher et al.   GENES & DEVELOPMENT

High serum level of fibroblast growth factor 21 is an independent predictor of non-alcoholic fatty liver disease: A 3-year prospective study in China

(2012) Huating Li et al.   JOURNAL OF HEPATOLOGY

FGF21 Promotes Metabolic Homeostasis via White Adipose and Leptin in Mice

(2012) Murielle M. Véniant et al.   PLoS One

Rationale-Based Engineering of a Potent Long-Acting FGF21 Analog for the Treatment of Type 2 Diabetes

(2012) Randy Hecht et al.   PLoS One

Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor  

(2012) W. Wei et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Treating Diabetes and Obesity with an FGF21-Mimetic Antibody Activating the  Klotho/FGFR1c Receptor Complex

(2012) I. N. Foltz et al.   Science Translational Medicine

The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue

(2012) Andrew C. Adams et al.   Molecular Metabolism

Integrated Regulation of Hepatic Metabolism by Fibroblast Growth Factor 21 (FGF21)in Vivo

(2011) ffolliott M. Fisher et al.   ENDOCRINOLOGY

Lack of Overt FGF21 Resistance in Two Mouse Models of Obesity and Insulin Resistance

(2011) Clarence Hale et al.   ENDOCRINOLOGY

Growth Hormone Induces Hepatic Production of Fibroblast Growth Factor 21 through a Mechanism Dependent on Lipolysis in Adipocytes

(2011) Wei Chen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Fibroblast Growth Factor 21 Induces Glucose Transporter-1 Expression through Activation of the Serum Response Factor/Ets-Like Protein-1 in Adipocytes

(2011) Xuan Ge et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans

(2010) Paul Lee et al.   AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

Fibroblast Growth Factor 21 Action in the Brain Increases Energy Expenditure and Insulin Sensitivity in Obese Rats

(2010) D. A. Sarruf et al.   DIABETES

Obesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State

(2010) f. M. Fisher et al.   DIABETES

Research Resource: Comprehensive Expression Atlas of the Fibroblast Growth Factor System in Adult Mouse

(2010) Klementina Fon Tacer et al.   MOLECULAR ENDOCRINOLOGY

Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse models—association with liver and adipose tissue effects

(2009) Jing Xu et al.   AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

Fibroblast Growth Factor 21 Controls Glycemia via Regulation of Hepatic Glucose Flux and Insulin Sensitivity

(2009) Eric D. Berglund et al.   ENDOCRINOLOGY

Fibroblast Growth Factor 21-Deficient Mice Demonstrate Impaired Adaptation to Ketosis

(2009) Michael K. Badman et al.   ENDOCRINOLOGY

Fibroblast Growth Factor 21 Regulates Lipolysis in White Adipose Tissue But Is Not Required for Ketogenesis and Triglyceride Clearance in Liver

(2009) Yuhei Hotta et al.   ENDOCRINOLOGY

Inhibition of lipolysis may contribute to the acute regulation of plasma FFA and glucose by FGF21 inob/obmice

(2009) Xiaofan Li et al.   FEBS LETTERS

Different roles of N- and C- termini in the functional activity of FGF21

(2009) Radmila Micanovic et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Circulating Fibroblast Growth Factor 21 Is Induced by Peroxisome Proliferator-Activated Receptor Agonists But Not Ketosis in Man

(2009) Constantinos Christodoulides et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Cold-Activated Brown Adipose Tissue in Healthy Men

(2009) Wouter D. van Marken Lichtenbelt et al.   NEW ENGLAND JOURNAL OF MEDICINE

FGF21 induces PGC-1  and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response

(2009) M. J. Potthoff et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Circulating Metabolic Regulator FGF21 Is Induced by Prolonged Fasting and PPARα Activation in Man

(2008) Cecilia Gälman et al.   Cell Metabolism

Serum FGF21 Levels Are Increased in Obesity and Are Independently Associated With the Metabolic Syndrome in Humans

(2008) X. Zhang et al.   DIABETES

Fibroblast Growth Factor 21 Reverses Hepatic Steatosis, Increases Energy Expenditure, and Improves Insulin Sensitivity in Diet-Induced Obese Mice

(2008) J. Xu et al.   DIABETES

Fibroblast Growth Factor 21 Corrects Obesity in Mice

(2008) Tamer Coskun et al.   ENDOCRINOLOGY

FGF21 attenuates lipolysis in human adipocytes - A possible link to improved insulin sensitivity

(2008) Peter Arner et al.   FEBS LETTERS

FGF21 N- and C-termini play different roles in receptor interaction and activation

(2008) Junming Yie et al.   FEBS LETTERS