Pirfenidone ameliorates MAFLD by improving insulin sensitivity and reducing epididymal fat

Introduction and Objectives: Metabolic associated fatty liver disease (MAFLD) is characterized by hepatic steatosis with the following three metabolic conditions: obesity/overweight, diabetes and metabolic dysregulation, either alone or in combination. Pirfenidone (PFD) has anti-inflammatory, antiox...

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Main Authors: J. Gutiérrez-Cuevas, D López-Cifuentes, AS Sandoval-Rodríguez, AO Vázquez-Esqueda, JS Rodríguez-Sanabria, J Armendáriz-Borunda
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Annals of Hepatology
Online Access:http://www.sciencedirect.com/science/article/pii/S1665268122002022
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author J. Gutiérrez-Cuevas
D López-Cifuentes
AS Sandoval-Rodríguez
AO Vázquez-Esqueda
JS Rodríguez-Sanabria
J Armendáriz-Borunda
author_facet J. Gutiérrez-Cuevas
D López-Cifuentes
AS Sandoval-Rodríguez
AO Vázquez-Esqueda
JS Rodríguez-Sanabria
J Armendáriz-Borunda
author_sort J. Gutiérrez-Cuevas
collection DOAJ
description Introduction and Objectives: Metabolic associated fatty liver disease (MAFLD) is characterized by hepatic steatosis with the following three metabolic conditions: obesity/overweight, diabetes and metabolic dysregulation, either alone or in combination. Pirfenidone (PFD) has anti-inflammatory, antioxidant, and anti-fibrotic effects. The aim of this study was to investigate the effects of PFD in mice with MAFLD induced by high-fat/high-carbohydrate (HFHC) diet. Materials and methods: At the age of 6-7 weeks, six male C57BL/6 J mice were fed with a normal diet (ND, 18% kcal from fat food) and twelve with HFHC (60% kcal from fat food and drinking water with 42 g/L of carbohydrates: 55% fructose and 45% sucrose) diet for 20 weeks; at 10 weeks of feeding, six mice with HFHC diet were administered PFD (300 mg/kg/day) by gavage. An insulin tolerance test was performed, and data analysis were performed using SPSS. The trial was approved by the research ethics committee. Results: All HFHC mice showed an increase in body weight and visceral fat accumulation (P<0.01), including elevated fasting glucose at week 20 (P<0.001). Liver weight and liver/body weight ratio exhibited no statistical significance. HFHC mice intervened with PFD showed reduced body weight gain (P=0.054) and epididymal fat pad weight (P<0.05). PFD also improved insulin resistance. Discussion: Obesity, systemic insulin resistance, and diabetes are commonly associated with MAFLD, which may progress to nonalcoholic steatohepatitis (NASH). PFD has been shown to have benefits in models of lipotoxicity and NASH. Conclusions: PFD could be a promising drug for the prevention and treatment of MAFLD induced by obesity. Funding: The resources used in this study were from the hospital without any additional financing Declaration of interest: The authors declare no potential conflicts of interest.
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spelling doaj.art-fb35025fe4a147918390875d3bacd5262022-12-22T04:36:00ZengElsevierAnnals of Hepatology1665-26812022-12-0127100860Pirfenidone ameliorates MAFLD by improving insulin sensitivity and reducing epididymal fatJ. Gutiérrez-Cuevas0D López-Cifuentes1AS Sandoval-Rodríguez2AO Vázquez-Esqueda3JS Rodríguez-Sanabria4J Armendáriz-Borunda5Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, Jalisco, MexicoDepartment of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, Jalisco, MexicoDepartment of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, Jalisco, MexicoDepartment of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, Jalisco, MexicoDepartment of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, Jalisco, MexicoDepartment of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, Jalisco, MexicoIntroduction and Objectives: Metabolic associated fatty liver disease (MAFLD) is characterized by hepatic steatosis with the following three metabolic conditions: obesity/overweight, diabetes and metabolic dysregulation, either alone or in combination. Pirfenidone (PFD) has anti-inflammatory, antioxidant, and anti-fibrotic effects. The aim of this study was to investigate the effects of PFD in mice with MAFLD induced by high-fat/high-carbohydrate (HFHC) diet. Materials and methods: At the age of 6-7 weeks, six male C57BL/6 J mice were fed with a normal diet (ND, 18% kcal from fat food) and twelve with HFHC (60% kcal from fat food and drinking water with 42 g/L of carbohydrates: 55% fructose and 45% sucrose) diet for 20 weeks; at 10 weeks of feeding, six mice with HFHC diet were administered PFD (300 mg/kg/day) by gavage. An insulin tolerance test was performed, and data analysis were performed using SPSS. The trial was approved by the research ethics committee. Results: All HFHC mice showed an increase in body weight and visceral fat accumulation (P<0.01), including elevated fasting glucose at week 20 (P<0.001). Liver weight and liver/body weight ratio exhibited no statistical significance. HFHC mice intervened with PFD showed reduced body weight gain (P=0.054) and epididymal fat pad weight (P<0.05). PFD also improved insulin resistance. Discussion: Obesity, systemic insulin resistance, and diabetes are commonly associated with MAFLD, which may progress to nonalcoholic steatohepatitis (NASH). PFD has been shown to have benefits in models of lipotoxicity and NASH. Conclusions: PFD could be a promising drug for the prevention and treatment of MAFLD induced by obesity. Funding: The resources used in this study were from the hospital without any additional financing Declaration of interest: The authors declare no potential conflicts of interest.http://www.sciencedirect.com/science/article/pii/S1665268122002022
spellingShingle J. Gutiérrez-Cuevas
D López-Cifuentes
AS Sandoval-Rodríguez
AO Vázquez-Esqueda
JS Rodríguez-Sanabria
J Armendáriz-Borunda
Pirfenidone ameliorates MAFLD by improving insulin sensitivity and reducing epididymal fat
Annals of Hepatology
title Pirfenidone ameliorates MAFLD by improving insulin sensitivity and reducing epididymal fat
title_full Pirfenidone ameliorates MAFLD by improving insulin sensitivity and reducing epididymal fat
title_fullStr Pirfenidone ameliorates MAFLD by improving insulin sensitivity and reducing epididymal fat
title_full_unstemmed Pirfenidone ameliorates MAFLD by improving insulin sensitivity and reducing epididymal fat
title_short Pirfenidone ameliorates MAFLD by improving insulin sensitivity and reducing epididymal fat
title_sort pirfenidone ameliorates mafld by improving insulin sensitivity and reducing epididymal fat
url http://www.sciencedirect.com/science/article/pii/S1665268122002022
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