FGF19 subfamily members: FGF19 and FGF21

Dolegowska, Katarzyna; Marchelek-Myśliwiec, Małgorzata; Nowosiad-Magda, Monika; Slawinski, Michal; Dołęgowska, Barbara

doi:10.1007/s13105-019-00675-7

Cited by 114 publications

(109 citation statements)

References 70 publications

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“…Other areas of investigation for fibrosis therapy in NASH include fibroblast growth factor (FGF). FGF19 is a pleotropic protein that has been shown to decrease gluconeogenesis and increase insulin sensitivity, inhibit fatty acid synthesis, increase hepatic synthesis of glycogen and proteins, and regulate bile acid homeostasis[ 58 ]. In a recent phase 2 study, Aldafermin (NGM282), a FGF19 analogue, demonstrated histological improvement in patients with NASH.…”

Section: Introductionmentioning

confidence: 99%

“…During the phase 2 trial, authors noted adverse gastrointestinal effects including nausea, abdominal pain, diarrhea and injection site reactions following administration of NGM282[ 60 ]. FGF21 is similar, as it plays many roles in metabolism, including fatty acid oxidation, lipolysis and gluconeogenesis[ 58 ]. Pegbelfermin (BMS-986036) is a pegylated human FGF21 analogue, and has shown a significant decrease in absolute hepatic fat fraction in the 10 mg daily group (-6.8% vs -1.3%; P = 0.0004) and in the 20 mg weekly subset (-5.2% vs -1.3%; P = 0.008) compared to placebo in patients with NASH fibrosis stages 1-3 (NCT02413372).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of anti-hepatic fibrosis drugs

Damiris

Tafesh

Pyrsopoulos

2020

WJG

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Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogenesis. Liver cirrhosis is the final result of prolonged fibrosis, which is an intimate balance between fibrogenesis and fibrinolysis. A number of these complex mechanisms are shared across the various etiologies of liver disease. Thankfully, investigation has yielded some promising results in regard to reversal of fibrosis, particularly the indirect benefits associated with antiviral therapy for the treatment of hepatitis B and C and the farnesoid receptor agonist for the treatment of primary biliary cholangitis and metabolic associated fatty liver disease. A majority of current clinical research is focused on targeting metabolic associated fatty liver disease and its progression to metabolic steatohepatitis and ultimately cirrhosis, with some hope of potential standardized therapeutics in the near future. With our ever-evolving understanding of the underlying pathophysiology, these therapeutics focus on either controlling the primary disease (the initial trigger of fibrogenesis), interrupting receptor ligand interactions and other intracellular communications, inhibiting fibrogenesis, or even promoting resolution of fibrosis. It is imperative to thoroughly test these potential therapies with the rigorous standards of clinical therapeutic trials in order to ensure the highest standards of patient safety. In this article we will briefly review the key pathophysiological pathways that lead to liver fibrosis and present current clinical and experimental evidence that has shown reversibility of liver fibrosis and cirrhosis, while commenting on therapeutic safety.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of anti-hepatic fibrosis drugs

Damiris

Tafesh

Pyrsopoulos

2020

WJG

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“…FGF19 is mainly secreted from the small intestine in response to food intake and exerts insulin-like effects: it promotes glycogen synthesis and inhibits gluconeogenesis. FGF21, on the other hand, is released from the liver in response to starvation and exhibits glucagon-like properties: it promotes lipolysis, thermogenesis and gluconeogenesis [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…It was previously shown that adult patients with obesity and metabolic diseases present reduced serum FGF19 levels with compensatory increases in FGF21 concentrations [7][8][9][10]. However, in children and adolescents, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly described [11,12].…”

Section: Introductionmentioning

confidence: 99%

Klotho and fibroblast growth factors 19 and 21 serum concentrations in children and adolescents with normal body weight and obesity and their associations with metabolic parameters

et al. 2020

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Background: Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components. Methods: This was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components. Results: The study was conducted with 174 children/adolescents aged 6-17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-bodyweight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score.

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“…The fibroblast growth factor (FGF) family has 22 members that are divided into further 7 subgroups based on phylogenetic similarity. FGFs function by binding to 4 tyrosine kinase receptors called FGF receptors (FGFRs) (1). FGF19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 that circulate in the blood and act on multiple organs involved in the regulation of metabolism.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women

et al. 2020

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Background: The fibroblast growth factors (FGF) 19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 are metabolic hormones involved in the regulation of glucose and lipid metabolism. Fetuin-A is a hepatokine involved in the regulation of beta-cell function and insulin resistance. Endocrine FGFs and fetuin-A are dysregulated in metabolic disorders including obesity, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome (PCOS). Our study was designed to examine the response of endocrine FGFs and fetuin-A to an acute intralipid, insulin infusion and exercise in PCOS and healthy women. Subjects and Measurements: Ten healthy and 11 PCOS subjects underwent 5-h saline infusions with a hyperinsulinemic-euglycemic clamp (HIEC) performed during the final 2 h. One week later, intralipid infusions were undertaken with a HIEC performed during the final 2 h. After an 8 week of exercise intervention the saline, intralipid, and HIEC were repeated. Plasma levels of endocrine FGFs and fetuin-A were measured. Results: Baseline fetuin-A was higher in PCOS women but FGF19, FGF21, and FGF23 did not differ and were unaffected by exercise. Insulin administration elevated FGF21 in control and PCOS, suppressed FGF19 in controls, and had no effects on FGF23 and fetuin-A. Intralipid infusion suppressed FGF19 and increased FGF21. Insulin with intralipid synergistically increased FGF21 and did not have effects on lipid-mediated suppression of FGF19 in both groups. Conclusion: Our study provides evidence for insulin and lipid regulation of endocrine FGFs in healthy and PCOS women, suggesting that FGF family members play a role in lipid and glucose metabolism.

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FGF19 subfamily members: FGF19 and FGF21

Cited by 114 publications

References 70 publications

Efficacy and safety of anti-hepatic fibrosis drugs

Efficacy and safety of anti-hepatic fibrosis drugs

Klotho and fibroblast growth factors 19 and 21 serum concentrations in children and adolescents with normal body weight and obesity and their associations with metabolic parameters

Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women

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