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Saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in Wistar rats: Plausible role of NLRP3 inflammasome and NF- κB

OBJECTIVE(S): Inflammation is the major progenitor of obesity and associated metabolic disorders. The current study investigated the modulatory role of saroglitazar on adipocyte dysfunction and associated inflammation in monosodium glutamate (MSG) obese Wistar rats. MATERIALS AND METHODS: The molecu...

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Autores principales: Nabi, Sayima, Bhandari, Uma, Haque, Syed Ehtaishamul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mashhad University of Medical Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392566/
https://www.ncbi.nlm.nih.gov/pubmed/36033946
http://dx.doi.org/10.22038/IJBMS.2022.64041.14102
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author Nabi, Sayima
Bhandari, Uma
Haque, Syed Ehtaishamul
author_facet Nabi, Sayima
Bhandari, Uma
Haque, Syed Ehtaishamul
author_sort Nabi, Sayima
collection PubMed
description OBJECTIVE(S): Inflammation is the major progenitor of obesity and associated metabolic disorders. The current study investigated the modulatory role of saroglitazar on adipocyte dysfunction and associated inflammation in monosodium glutamate (MSG) obese Wistar rats. MATERIALS AND METHODS: The molecular docking simulation studies of saroglitazar and fenofibrate were performed on the ligand-binding domain of NLRP3 and NF- κB. Under in vivo study, neonatal pups received normal saline or MSG (4 g/kg, SC) for 7 alternate days after birth. After keeping for 42 days as such, animals were divided into seven groups: Normal control; MSG control; MSG + saroglitazar (2 mg/kg); MSG + saroglitazar (4 mg/kg); saroglitazar (4 mg/kg) per se; MSG + fenofibrate (100 mg/kg); fenofibrate (100 mg/kg) per se. Drug treatments were given orally, from the 42(nd) to 70(th) day. On day 71, blood was collected and animals were sacrificed for isolation of liver and fat pads. RESULTS: In silico study showed significant binding of saroglitazar and fenofibrate against NLRP3 and NF- κB. Saroglitazar significantly reduced body weight, body mass index, Lee’s index, fat pad weights, adiposity index, decreased serum lipids, interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), leptin, insulin, blood glucose, HOMA-IR values, oxidative stress in the liver and increased hepatic low-density lipoprotein receptor levels. Histopathological analysis of the liver showed decreased inflammation and vacuolization, and reduced adipocyte cell size. Immunohistochemical analysis showed suppression of NLRP3 in epididymal adipocytes and NF- κB expression in the liver. CONCLUSION: Saroglitazar ameliorated obesity and associated inflammation via modulation of NLRP3 inflammasome and NF- κB in MSG obese Wistar rats.
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spelling pubmed-93925662022-08-26 Saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in Wistar rats: Plausible role of NLRP3 inflammasome and NF- κB Nabi, Sayima Bhandari, Uma Haque, Syed Ehtaishamul Iran J Basic Med Sci Original Article OBJECTIVE(S): Inflammation is the major progenitor of obesity and associated metabolic disorders. The current study investigated the modulatory role of saroglitazar on adipocyte dysfunction and associated inflammation in monosodium glutamate (MSG) obese Wistar rats. MATERIALS AND METHODS: The molecular docking simulation studies of saroglitazar and fenofibrate were performed on the ligand-binding domain of NLRP3 and NF- κB. Under in vivo study, neonatal pups received normal saline or MSG (4 g/kg, SC) for 7 alternate days after birth. After keeping for 42 days as such, animals were divided into seven groups: Normal control; MSG control; MSG + saroglitazar (2 mg/kg); MSG + saroglitazar (4 mg/kg); saroglitazar (4 mg/kg) per se; MSG + fenofibrate (100 mg/kg); fenofibrate (100 mg/kg) per se. Drug treatments were given orally, from the 42(nd) to 70(th) day. On day 71, blood was collected and animals were sacrificed for isolation of liver and fat pads. RESULTS: In silico study showed significant binding of saroglitazar and fenofibrate against NLRP3 and NF- κB. Saroglitazar significantly reduced body weight, body mass index, Lee’s index, fat pad weights, adiposity index, decreased serum lipids, interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), leptin, insulin, blood glucose, HOMA-IR values, oxidative stress in the liver and increased hepatic low-density lipoprotein receptor levels. Histopathological analysis of the liver showed decreased inflammation and vacuolization, and reduced adipocyte cell size. Immunohistochemical analysis showed suppression of NLRP3 in epididymal adipocytes and NF- κB expression in the liver. CONCLUSION: Saroglitazar ameliorated obesity and associated inflammation via modulation of NLRP3 inflammasome and NF- κB in MSG obese Wistar rats. Mashhad University of Medical Sciences 2022-07 /pmc/articles/PMC9392566/ /pubmed/36033946 http://dx.doi.org/10.22038/IJBMS.2022.64041.14102 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Nabi, Sayima
Bhandari, Uma
Haque, Syed Ehtaishamul
Saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in Wistar rats: Plausible role of NLRP3 inflammasome and NF- κB
title Saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in Wistar rats: Plausible role of NLRP3 inflammasome and NF- κB
title_full Saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in Wistar rats: Plausible role of NLRP3 inflammasome and NF- κB
title_fullStr Saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in Wistar rats: Plausible role of NLRP3 inflammasome and NF- κB
title_full_unstemmed Saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in Wistar rats: Plausible role of NLRP3 inflammasome and NF- κB
title_short Saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in Wistar rats: Plausible role of NLRP3 inflammasome and NF- κB
title_sort saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in wistar rats: plausible role of nlrp3 inflammasome and nf- κb
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392566/
https://www.ncbi.nlm.nih.gov/pubmed/36033946
http://dx.doi.org/10.22038/IJBMS.2022.64041.14102
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