Efficacy of fibroblast growth factor 21 in non‐alcoholic fatty liver disease in guinea pigs

Klaebel, Julie Hviid; Lykkesfeldt, Jens; Tveden‐Nyborg, Pernille

doi:10.1111/bcpt.13705

Cited by 3 publications

(2 citation statements)

References 32 publications

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“… Pan (2021) 35 a) Male C57BL/6 mice on HFD b) SD rats GLP-1-Fc-FGF-21 dual agonist vs GLP-1 vs FGF-21 monoagonist administration 6 Greater reduction in steatosis, inflammation, hepatocellular ballooning and NAS after GLP-1-Fc-FGF-21 compared to GLP-1 or FGF-21. Klaebel (2022) 39 Female guinea pigs on HFD Recombinant native human FGF-21 vs chimeric human recombinant analog FGF-21/19 2–6 Reduced liver weight and attenuation of dyslipidemia after treatment with the chimeric agonist compared to native FGF-21. Puengel (2022) 38 Male C57BL/6J mice on CDAHFD CCR2/5 inhibitor (BMS-687681-02-020) vs PEGylated FGF-21 agonist (BMS-986171) vs their combination 12 Reduced HFC and NAS, but no significant changes in fibrosis with the FGF-21 agonist.…”

Section: Experimental Studiesmentioning

confidence: 99%

“… 22 , 27 , 31–37 More interestingly, other authors reported that monotherapy with FGF-21 or a glucagon-like peptide-1 receptor agonist (GLP-1RA) had an inferior effect on hepatic histology than a GLP-1-Fc-FGF-21 dual agonist, 35 that the combination of an FGF-21 analog with a C–C motif chemokine receptor 2/5 (CCR2/5) inhibitor had also greater effect on hepatic steatosis and NASH than either monotherapy, 38 and that a chimeric FGF-21/FGF-19 analog reduced liver weight more than FGF-21 monotherapy. 39 …”

Section: Experimental Studiesmentioning

confidence: 99%

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Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Raptis¹,

Mantzoros²,

Polyzos³

2023

TCRM

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Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease without any approved treatment to-date despite intensive research efforts by researchers and pharmaceutical industry. Fibroblast growth factor (FGF)-21 has been gaining increasing attention as a possible contributing factor and thus therapeutic target for obesity-related metabolic disorders, including NAFLD, mainly due to its effects on lipid and carbohydrate metabolism. Most animal and human observational studies have shown higher FGF-21 concentrations in NAFLD than non-NAFLD, implying that FGF-21 may be increased to counteract hepatic steatosis and inflammation. However, although Mendelian Randomization studies have revealed that variations of FGF-21 levels within the physiological range may have effects in hyperlipidemia and possibly nonalcoholic steatohepatitis, they also indicate that FGF-21, in physiological concentrations, may fail to reverse NAFLD and may not be able to control obesity and other diseases, indicating a state of FGF-21 resistance or insensitivity that could not respond to administration of FGF-21 in supraphysiological concentrations. Interventional studies with FGF-21 analogs (eg, pegbelfermin, efruxifermin, BOS-580) in humans have provided some favorable results in Phase 1 and Phase 2 studies. However, the definite effect of FGF-21 on NAFLD may be clarified after the completion of the ongoing clinical trials with paired liver biopsies and histological endpoints. The aim of this review is to critically summarize experimental and clinical data of FGF-21 in NAFLD, in an attempt to highlight existing knowledge and areas of uncertainty, and subsequently, to focus on the potential therapeutic effects of FGF-21 and its analogs in NAFLD.

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Section: Experimental Studiesmentioning

confidence: 99%

Section: Experimental Studiesmentioning

confidence: 99%

Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Raptis¹,

Mantzoros²,

Polyzos³

2023

TCRM

View full text Add to dashboard Cite

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Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

Poulsen

et al. 2022

Sig Transduct Target Ther

131

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Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, and fibrosis. Importantly, growing evidence elucidates that the disruption of the gut–liver axis and microbe-derived metabolites drive the pathogenesis of NAFL/NASH. Extracellular vesicles (EVs) act as a signaling mediator, resulting in lipid accumulation, macrophage and hepatic stellate cell activation, further promoting inflammation and liver fibrosis progression during the development of NAFL/NASH. Targeting gut microbiota or EVs may serve as new strategies for the treatment of NAFL/NASH. Finally, other mechanisms, such as cell therapy and genetic approaches, also have enormous therapeutic potential. Incorporating drugs with different mechanisms and personalized medicine may improve the efficacy to better benefit patients with NAFL/NASH.

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Thymus atlanticus (Ball) Roussine Aqueous Extract Exerts Lipid-lowering and Anti-atherosclerotic Effects in Hyperlipidemic Guinea Pigs

Elbouny,

Ouahzizi,

Bekkouch

et al. 2023

CHDDT

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Background:: Thymus atlanticus (Ball) Roussine (T. atlanticus) is traditionally used in the Moroccan high Atlas Mountains to treat several disorders, including cardiovascular disease. In the present study, the lipid-lowering and anti-atherosclerotic activities of the traditionally used aqueous extract of T. atlanticus were evaluated on guinea pigs subjected to chronic hyperlipidemia. Methods:: Animals were given a diet containing 2% cholesterol and 20% lard for 12 weeks. Moreover, thyme extract was given daily at 400 mg/kg. At the end of the experiment, lipid levels and paraoxonase arylesterase activity were measured, and aorta histology was studied. Results:: Our findings revealed that there was an important elevation of blood lipids in the HFD group along with a significant decrease in paraoxonase arylesterase activity (-40.06%). Moreover, the consumption of fat altered the histology of aorta by thickening the intima media and forming atherosclerotic lesions and foam cells in these tissues. However, the administration of thyme extract attenuated HFD-caused alterations by decreasing blood lipids, elevating paraoxonase activity (+24.04%), and limiting the progression of atherosclerotic lesions. Conclusion:: We conclude that the supplementation with the aqueous extract of T. atlanticus could potentially protect against hyperlipidemia and consequently, the development of atherosclerosis

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Efficacy of fibroblast growth factor 21 in non‐alcoholic fatty liver disease in guinea pigs

Cited by 3 publications

References 32 publications

Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

Thymus atlanticus (Ball) Roussine Aqueous Extract Exerts Lipid-lowering and Anti-atherosclerotic Effects in Hyperlipidemic Guinea Pigs

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