Ursolic acid attenuates obesity-related metabolic dysfunction via modulation of peroxisome proliferator activated receptor-gamma in male Wistar rats fed with high-carbohydrate high-fat diet
Abstract Background The risk factors of metabolic syndrome (MS) precedes the development of cardiovascular disease and type 2 diabetes and are largely triggered by high-carbohydrate high-fat diet (HCHFD) and sedentary lifestyle. The development of these risk factors is connected to persistent low-gr...
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2025-01-01
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Series: | Beni-Suef University Journal of Basic and Applied Sciences |
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Online Access: | https://doi.org/10.1186/s43088-024-00565-y |
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author | Oluwatosin O. Omodara Mohammed U. Kawu Ibrahim G. Bako Daniel H. Mhya Theophilus T. Dawus |
author_facet | Oluwatosin O. Omodara Mohammed U. Kawu Ibrahim G. Bako Daniel H. Mhya Theophilus T. Dawus |
author_sort | Oluwatosin O. Omodara |
collection | DOAJ |
description | Abstract Background The risk factors of metabolic syndrome (MS) precedes the development of cardiovascular disease and type 2 diabetes and are largely triggered by high-carbohydrate high-fat diet (HCHFD) and sedentary lifestyle. The development of these risk factors is connected to persistent low-grade inflammation. Though, ursolic acid (UA) has been shown to prevent HCHFD-induced metabolic parameters. The present study aimed to elucidate the molecular mechanisms underlying the preventive effects of dietary UA supplementation on obesity-related metabolic disorders and inflammation in male Wistar rats fed with HCHFD. The animals were randomly divided into 4 groups (n = 5): 1—normal diet (ND) + distilled water (DW); 2—ND + UA; 3—HCHFD + DW; 4—HCHFD + UA. HCHFD was augmented with 20% fructose in drinking water. The animals were fed their respective diets daily for 20 weeks. 250 mg/kg body weight of ursolic acid was administered orally to UA-treated groups for the last 8 weeks. Blood samples were collected and liver and adipose tissues were harvested for biochemical and tissue analysis, respectively. Results BMI and FBG were significantly lowered in the HCHFD + UA-fed animals compared to the HCHFD + DW-fed animals. In the HCHFD + UA-fed animals, HOMA-IR, serum insulin, cholesterol, triglyceride and low-density lipoprotein cholesterol (LDL-C) were significantly decreased while high-density lipoprotein cholesterol (HDL-C) was increased compared to the HCHFD + DW-fed animals. UA significantly decreased serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and increased adiponectin level compared to the HCHFD + DW-fed animals. The messenger ribonucleic acid (mRNA) level of peroxisome proliferator activated receptor-gamma (PPAR-γ) in adipose tissue was significantly upregulated while liver PPAR-γ mRNA level was significantly downregulated in HCHFD + UA-fed animals compared to HCHFD + DW group, respectively. UA restored the architecture of liver parenchyma to near normal. Conclusion Dietary UA supplementation mitigated metabolic dysfunction and inflammation associated with obesity via modulation of liver and adipose tissue PPAR-γ in male Wistar rats fed with HCHFD for 20 weeks. |
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institution | Kabale University |
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spelling | doaj-art-3557e2c0c77e4835b4e03d76902f8d1f2025-01-12T12:35:19ZengSpringerOpenBeni-Suef University Journal of Basic and Applied Sciences2314-85432025-01-0114111210.1186/s43088-024-00565-yUrsolic acid attenuates obesity-related metabolic dysfunction via modulation of peroxisome proliferator activated receptor-gamma in male Wistar rats fed with high-carbohydrate high-fat dietOluwatosin O. Omodara0Mohammed U. Kawu1Ibrahim G. Bako2Daniel H. Mhya3Theophilus T. Dawus4Department of Human Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, Abubakar Tafawa Balewa UniversityDepartment of Veterinary Physiology, Faculty of Veterinary Medicine, Ahmadu Bello UniversityDepartment of Human Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, Ahmadu Bello UniversityDepartment of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Medical Sciences, Abubakar Tafawa Balewa UniversityDepartment of Human Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Abubakar Tafawa Balewa UniversityAbstract Background The risk factors of metabolic syndrome (MS) precedes the development of cardiovascular disease and type 2 diabetes and are largely triggered by high-carbohydrate high-fat diet (HCHFD) and sedentary lifestyle. The development of these risk factors is connected to persistent low-grade inflammation. Though, ursolic acid (UA) has been shown to prevent HCHFD-induced metabolic parameters. The present study aimed to elucidate the molecular mechanisms underlying the preventive effects of dietary UA supplementation on obesity-related metabolic disorders and inflammation in male Wistar rats fed with HCHFD. The animals were randomly divided into 4 groups (n = 5): 1—normal diet (ND) + distilled water (DW); 2—ND + UA; 3—HCHFD + DW; 4—HCHFD + UA. HCHFD was augmented with 20% fructose in drinking water. The animals were fed their respective diets daily for 20 weeks. 250 mg/kg body weight of ursolic acid was administered orally to UA-treated groups for the last 8 weeks. Blood samples were collected and liver and adipose tissues were harvested for biochemical and tissue analysis, respectively. Results BMI and FBG were significantly lowered in the HCHFD + UA-fed animals compared to the HCHFD + DW-fed animals. In the HCHFD + UA-fed animals, HOMA-IR, serum insulin, cholesterol, triglyceride and low-density lipoprotein cholesterol (LDL-C) were significantly decreased while high-density lipoprotein cholesterol (HDL-C) was increased compared to the HCHFD + DW-fed animals. UA significantly decreased serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and increased adiponectin level compared to the HCHFD + DW-fed animals. The messenger ribonucleic acid (mRNA) level of peroxisome proliferator activated receptor-gamma (PPAR-γ) in adipose tissue was significantly upregulated while liver PPAR-γ mRNA level was significantly downregulated in HCHFD + UA-fed animals compared to HCHFD + DW group, respectively. UA restored the architecture of liver parenchyma to near normal. Conclusion Dietary UA supplementation mitigated metabolic dysfunction and inflammation associated with obesity via modulation of liver and adipose tissue PPAR-γ in male Wistar rats fed with HCHFD for 20 weeks.https://doi.org/10.1186/s43088-024-00565-yUrsolic acidMetabolic syndromeObesityHigh-carbohydrate high-fat diet20 weeksInsulin resistance |
spellingShingle | Oluwatosin O. Omodara Mohammed U. Kawu Ibrahim G. Bako Daniel H. Mhya Theophilus T. Dawus Ursolic acid attenuates obesity-related metabolic dysfunction via modulation of peroxisome proliferator activated receptor-gamma in male Wistar rats fed with high-carbohydrate high-fat diet Beni-Suef University Journal of Basic and Applied Sciences Ursolic acid Metabolic syndrome Obesity High-carbohydrate high-fat diet 20 weeks Insulin resistance |
title | Ursolic acid attenuates obesity-related metabolic dysfunction via modulation of peroxisome proliferator activated receptor-gamma in male Wistar rats fed with high-carbohydrate high-fat diet |
title_full | Ursolic acid attenuates obesity-related metabolic dysfunction via modulation of peroxisome proliferator activated receptor-gamma in male Wistar rats fed with high-carbohydrate high-fat diet |
title_fullStr | Ursolic acid attenuates obesity-related metabolic dysfunction via modulation of peroxisome proliferator activated receptor-gamma in male Wistar rats fed with high-carbohydrate high-fat diet |
title_full_unstemmed | Ursolic acid attenuates obesity-related metabolic dysfunction via modulation of peroxisome proliferator activated receptor-gamma in male Wistar rats fed with high-carbohydrate high-fat diet |
title_short | Ursolic acid attenuates obesity-related metabolic dysfunction via modulation of peroxisome proliferator activated receptor-gamma in male Wistar rats fed with high-carbohydrate high-fat diet |
title_sort | ursolic acid attenuates obesity related metabolic dysfunction via modulation of peroxisome proliferator activated receptor gamma in male wistar rats fed with high carbohydrate high fat diet |
topic | Ursolic acid Metabolic syndrome Obesity High-carbohydrate high-fat diet 20 weeks Insulin resistance |
url | https://doi.org/10.1186/s43088-024-00565-y |
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