The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy

Liu, Jia; Xu, Yuan; Hu, Yanjin; Wang, Guang

doi:10.1016/j.metabol.2014.11.009

Cited by 104 publications

(79 citation statements)

References 97 publications

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“…PPARα activation increases FGF21 levels. FGF21 improves energy production by increasing the utilization of fatty acids (51) and is a potent inhibitor of hepatic steatosis (52). Our results showed that FGF21 levels were elevated in Arv1 -/ -animals.…”

Section: Arv1supporting

confidence: 53%

Mice lacking have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease

Gallo-Ebert¹,

Francisco²,

Liu³

et al. 2018

Journal of Biological Chemistry

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Section: Arv1supporting

confidence: 53%

Mice lacking have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease

Gallo-Ebert¹,

Francisco²,

Liu³

et al. 2018

Journal of Biological Chemistry

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“…Several recent studies reported that FGF21 could play a role in the progression of NAFLD by decreasing inflammation, cytokine levels, and oxidative stress. 20) Moreover, it has been reported that PPARα-mediated FGF21 expression stimulates the thermogenic activation of brown adipose tissue (BAT) and WAT leading to the improvement of metabolic syndromes, such as NAFLD and insulin resistance. 21) As observed in our previous study that MHY2013 markedly increased the expression of WAT browning markers and formation of multilocular lipid droplets in the WAT of db/db mice as well as 3T3-L1 adipocyte, 12) we assume that MHY2013 has the potential to stimulate thermogenic activation of BAT and WAT in aged rats.…”

Section: Discussionmentioning

confidence: 99%

A PPAR Pan Agonist, MHY2013 Alleviates Age-Related Hepatic Lipid Accumulation by Promoting Fatty Acid Oxidation and Suppressing Inflammation

Lee

Kim

et al. 2018

Biological & Pharmaceutical Bulletin

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Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Peroxisome proliferator-activated receptors (PPARs) play a role in regulating hepatic lipid accumulation, a hallmark of NAFLD development. A PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013) has been shown to prevent fatty liver formation and insulin resistance in obese mice (db/db) model. However, the beneficial effects of MHY2013 in aged model remain unknown. In this study, we investigated whether MHY2013 alleviates hepatic lipid accumulation in aged Sprague-Dawley (SD) rats. We confirmed that MHY2013 increased the activities of three PPAR subtypes in HepG2 cells using luciferase assay. When administered orally in aged SD rats, MHY2013 markedly decreased the hepatic triglyceride levels without changes in body weight. Regarding underlying mechanisms, MHY2013 increased the mRNA levels of lipid oxidation-related genes, including carnitine palmitoyltransferase 1 (CPT1) and peroxisomal acyl-CoA oxidase 1 (ACOX1), without apparent change in the mRNA expression of lipogenesis-related genes. Furthermore, MHY2013 significantly increased systemic fibroblast growth factor 21 (FGF21) and adiponectin levels and suppressed inflammatory mRNA expression in the liver. In conclusion, MHY2013 alleviated age-related hepatic lipid accumulation, in part by upregulating β-oxidation signaling and suppressing inflammation in the liver. Therefore, MHY2013 is a potential pharmaceutical agent for treating age-related hepatic lipid accumulation.Key words aging; nonalcoholic fatty liver disease; MHY2013; peroxisome proliferator-activated receptor (PPAR) pan agonist; lipid oxidation Aging of vast majority of population is very recent phenomenon that has emerged as a direct consequence of the extension of lifespan. The aging process cause hepatic functional and structural impairments leading to metabolic risks.

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“…Furthermore, FGF21 leads to a decrease in free fatty acids by inhibiting lipolysis in adipose tissue (167). FGF21 has been reported to attenuate hepatic steatosis in animal models and therefore may serve as a novel therapeutic approach (168)(169)(170)(171)(172); pegylated FGF21 (BMS-986036) is currently under investigation in NASH patients (NCT02413372).…”

Section: Different Underlying Pathophysiologies and Therapeutic Implimentioning

confidence: 99%

Therapeutic opportunities for alcoholic steatohepatitis and nonalcoholic steatohepatitis: exploiting similarities and differences in pathogenesis

et al. 2017

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The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy

Cited by 104 publications

References 97 publications

Mice lacking have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease

Mice lacking have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease

A PPAR Pan Agonist, MHY2013 Alleviates Age-Related Hepatic Lipid Accumulation by Promoting Fatty Acid Oxidation and Suppressing Inflammation

Therapeutic opportunities for alcoholic steatohepatitis and nonalcoholic steatohepatitis: exploiting similarities and differences in pathogenesis

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