Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet

Abdulrasheed O Abdulrahman,1 Abudukadeer Kuerban,1 Zuhair Ahmed Alshehri,1 Wesam H Abdulaal,1 Jalaluddin Awlia Khan,1 Mohammad Imran Khan1,2 1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 2Cancer Metabolism and Epigenetic Unit, Faculty of Scie...

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Autores principales:	Abdulrahman AO, Kuerban A, Alshehri ZA, Abdulaal WH, Khan JA, Khan MI
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	de novo lipogenesis er stress high-fat diet obesity pomegranate urolithins Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/b0a49d2083da4ad5b12757760ae33336
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spelling	oai:doaj.org-article:b0a49d2083da4ad5b12757760ae333362021-12-02T10:05:06ZUrolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet1178-7007https://doaj.org/article/b0a49d2083da4ad5b12757760ae333362020-09-01T00:00:00Zhttps://www.dovepress.com/urolithins-attenuate-multiple-symptoms-of-obesity-in-rats-fed-on-a-hig-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Abdulrasheed O Abdulrahman,1 Abudukadeer Kuerban,1 Zuhair Ahmed Alshehri,1 Wesam H Abdulaal,1 Jalaluddin Awlia Khan,1 Mohammad Imran Khan1,2 1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 2Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaCorrespondence: Mohammad Imran KhanDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaTel +966-12-6952000Email mikhan@kau.edu.saBackground: Urolithins are gut microbiota-derived polyphenol metabolites, produced following the consumption of pomegranate, berries, and nuts. Recent studies have shown the potentials of these metabolites on reducing triglycerides accumulation in cultured hepatocytes and adipocytes. In this study, we investigated the ability of both urolithin A (Uro-A) and urolithin B (Uro-B) to attenuate obesity and associated symptoms in a high-fat diet-induced obesity model in rats.Methods: Twenty-four male Wistar rats were randomly assigned to four groups. Group 1 was fed on a normal diet while groups 2, 3, and 4 were fed on a high-fat diet for 10 weeks. After this, groups 3 and 4 were treated with 2.5mg/kg body weight of Uro-A and Uro-B intraperitoneally, respectively. Body weight, serum lipid profile, hepatic antioxidant activity, hepatic lipid accumulation, fecal lipid content, and the expressions of genes involved in lipogenesis and hepatic ER stress were quantified.Results: Indeed, a high-fat diet resulted in increased body weight, visceral adipose tissue mass, and oxidative stress in rats. However, treatment with both Uro-A and Uro-B decreased body weight and visceral adipose tissue mass. These metabolites restored hepatic antioxidant capacity and decreased lipid accumulation in addition to an increase in fecal fat excretion. Moreover, both Uro-A and Uro-B treatment downregulated the expression of LXRα and SREBP1c; involved in de novo lipogenesis while upregulating PPARα expression for increased fatty acid oxidation. Furthermore, Uro-A and Uro-B decreased the expression of PERK and IRE1α; which are involved in hepatic ER stress. Taken together, our results showed the potentials of Uro-A and Uro-B in mitigating obesity symptoms and they could thus provide promising roles in the future as functional anti-obesity candidates.Keywords: de novo lipogenesis, ER stress, high-fat diet, obesity, pomegranate, urolithinsAbdulrahman AOKuerban AAlshehri ZAAbdulaal WHKhan JAKhan MIDove Medical Pressarticlede novo lipogenesiser stresshigh-fat dietobesitypomegranateurolithinsSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 3337-3348 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	de novo lipogenesis er stress high-fat diet obesity pomegranate urolithins Specialties of internal medicine RC581-951
spellingShingle	de novo lipogenesis er stress high-fat diet obesity pomegranate urolithins Specialties of internal medicine RC581-951 Abdulrahman AO Kuerban A Alshehri ZA Abdulaal WH Khan JA Khan MI Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet
description	Abdulrasheed O Abdulrahman,1 Abudukadeer Kuerban,1 Zuhair Ahmed Alshehri,1 Wesam H Abdulaal,1 Jalaluddin Awlia Khan,1 Mohammad Imran Khan1,2 1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 2Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaCorrespondence: Mohammad Imran KhanDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaTel +966-12-6952000Email mikhan@kau.edu.saBackground: Urolithins are gut microbiota-derived polyphenol metabolites, produced following the consumption of pomegranate, berries, and nuts. Recent studies have shown the potentials of these metabolites on reducing triglycerides accumulation in cultured hepatocytes and adipocytes. In this study, we investigated the ability of both urolithin A (Uro-A) and urolithin B (Uro-B) to attenuate obesity and associated symptoms in a high-fat diet-induced obesity model in rats.Methods: Twenty-four male Wistar rats were randomly assigned to four groups. Group 1 was fed on a normal diet while groups 2, 3, and 4 were fed on a high-fat diet for 10 weeks. After this, groups 3 and 4 were treated with 2.5mg/kg body weight of Uro-A and Uro-B intraperitoneally, respectively. Body weight, serum lipid profile, hepatic antioxidant activity, hepatic lipid accumulation, fecal lipid content, and the expressions of genes involved in lipogenesis and hepatic ER stress were quantified.Results: Indeed, a high-fat diet resulted in increased body weight, visceral adipose tissue mass, and oxidative stress in rats. However, treatment with both Uro-A and Uro-B decreased body weight and visceral adipose tissue mass. These metabolites restored hepatic antioxidant capacity and decreased lipid accumulation in addition to an increase in fecal fat excretion. Moreover, both Uro-A and Uro-B treatment downregulated the expression of LXRα and SREBP1c; involved in de novo lipogenesis while upregulating PPARα expression for increased fatty acid oxidation. Furthermore, Uro-A and Uro-B decreased the expression of PERK and IRE1α; which are involved in hepatic ER stress. Taken together, our results showed the potentials of Uro-A and Uro-B in mitigating obesity symptoms and they could thus provide promising roles in the future as functional anti-obesity candidates.Keywords: de novo lipogenesis, ER stress, high-fat diet, obesity, pomegranate, urolithins
format	article
author	Abdulrahman AO Kuerban A Alshehri ZA Abdulaal WH Khan JA Khan MI
author_facet	Abdulrahman AO Kuerban A Alshehri ZA Abdulaal WH Khan JA Khan MI
author_sort	Abdulrahman AO
title	Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet
title_short	Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet
title_full	Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet
title_fullStr	Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet
title_full_unstemmed	Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet
title_sort	urolithins attenuate multiple symptoms of obesity in rats fed on a high-fat diet
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/b0a49d2083da4ad5b12757760ae33336
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Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet

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