Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats

Background: The harmful consequences of non-alcoholic fatty liver disease (NAFLD) are posing an increasing threat to public health as the incidence of diabetes and obesity increases globally. A non-invasive treatment with a range of autonomic and metabolic benefits is transcutaneous vagus nerve stim...

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Main Authors: Hany A. Elkattawy, Samar Mortada Mahmoud, Ahmed El-Sayed Hassan, Ahmed Behiry, Hasnaa Ali Ebrahim, Ateya Megahed Ibrahim, Donia Elsaid Fathi Zaghamir, Mohamed El-Sherbiny, Sherein F. El-Sayed
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/12/3255
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author Hany A. Elkattawy
Samar Mortada Mahmoud
Ahmed El-Sayed Hassan
Ahmed Behiry
Hasnaa Ali Ebrahim
Ateya Megahed Ibrahim
Donia Elsaid Fathi Zaghamir
Mohamed El-Sherbiny
Sherein F. El-Sayed
author_facet Hany A. Elkattawy
Samar Mortada Mahmoud
Ahmed El-Sayed Hassan
Ahmed Behiry
Hasnaa Ali Ebrahim
Ateya Megahed Ibrahim
Donia Elsaid Fathi Zaghamir
Mohamed El-Sherbiny
Sherein F. El-Sayed
author_sort Hany A. Elkattawy
collection DOAJ
description Background: The harmful consequences of non-alcoholic fatty liver disease (NAFLD) are posing an increasing threat to public health as the incidence of diabetes and obesity increases globally. A non-invasive treatment with a range of autonomic and metabolic benefits is transcutaneous vagus nerve stimulation (tVNS). Aim of the study: To investigate the possible preventive impacts of VNS against adult rats’ NAFLD caused by a high-fat diet (HFD) and to clarify the underlying mechanisms. Methods: A total of thirty-two adult male rats were split into two groups: the HFD-induced NAFLD group (<i>n</i> = 24) and the control normal group (<i>n</i> = 8). The obesogenic diet was maintained for 12 weeks to induce hepatic steatosis. The HFD-induced NAFLD group (<i>n</i> = 24) was separated into three groups: the group without treatment (<i>n</i> = 8), the group with sham stimulation (<i>n</i> = 8), and the group with VNS treatment (<i>n</i> = 8). VNS was delivered for 30 min per day for 6 weeks after the establishment of NAFLD using a digital TENS device. The subsequent assessments included hepatic triglyceride, cholesterol content, serum lipid profile, and liver function testing. In this context, inflammatory biomarkers (TNF-α, IL-6) and hepatic oxidative stress (MDA, SOD, and GPx) were also assessed. To clarify the possible mechanisms behind the protective benefits of VNS, additional histological inspection and immunohistochemistry analysis of TNF-α and Caspase-3 were performed. Results: In the NAFLD-affected obese rats, VNS markedly decreased the rats’ body mass index (BMI) and abdominal circumference (AC). Liver function markers (albumin, ALT, and AST) and the serum lipid profile—which included a notable decrease in the amounts of hepatic triglycerides and cholesterol—were both markedly improved. Additionally, oxidative stress and inflammatory indicators showed a considerable decline with VNS. Notably, the liver tissues examined by histopathologists revealed that there is evidence of the protective impact of VNS on the oxidative and inflammatory states linked to HFD-induced NAFLD while maintaining the architectural and functional condition of the liver. Conclusions: Our findings suggest that VNS may represent a promising therapeutic candidate for managing NAFLD induced by obesity. It can be considered to be an effective adjuvant physiological intervention for the obese population with NAFLD to spare the liver against obesity-induced deleterious injury.
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spelling doaj.art-e36d94a696334f52bf9dfc1451f15cdf2023-12-22T13:55:06ZengMDPI AGBiomedicines2227-90592023-12-011112325510.3390/biomedicines11123255Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in RatsHany A. Elkattawy0Samar Mortada Mahmoud1Ahmed El-Sayed Hassan2Ahmed Behiry3Hasnaa Ali Ebrahim4Ateya Megahed Ibrahim5Donia Elsaid Fathi Zaghamir6Mohamed El-Sherbiny7Sherein F. El-Sayed8Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 11579, Saudi ArabiaDepartment of Human Anatomy and Embryology, College of Medicine, Zagazig University, Zagazig P.O. Box 44519, EgyptMedical Physiology Department, College of Medicine, Zagazig University, Zagazig P.O. Box 44519, EgyptDepartment of Tropical Medicine and Endemic Diseases, College of Medicine, Zagazig University, Zagazig P.O. Box 44519, EgyptDepartment of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi ArabiaDepartment of Nursing, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Nursing, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 11579, Saudi ArabiaMedical Physiology Department, College of Medicine, Zagazig University, Zagazig P.O. Box 44519, EgyptBackground: The harmful consequences of non-alcoholic fatty liver disease (NAFLD) are posing an increasing threat to public health as the incidence of diabetes and obesity increases globally. A non-invasive treatment with a range of autonomic and metabolic benefits is transcutaneous vagus nerve stimulation (tVNS). Aim of the study: To investigate the possible preventive impacts of VNS against adult rats’ NAFLD caused by a high-fat diet (HFD) and to clarify the underlying mechanisms. Methods: A total of thirty-two adult male rats were split into two groups: the HFD-induced NAFLD group (<i>n</i> = 24) and the control normal group (<i>n</i> = 8). The obesogenic diet was maintained for 12 weeks to induce hepatic steatosis. The HFD-induced NAFLD group (<i>n</i> = 24) was separated into three groups: the group without treatment (<i>n</i> = 8), the group with sham stimulation (<i>n</i> = 8), and the group with VNS treatment (<i>n</i> = 8). VNS was delivered for 30 min per day for 6 weeks after the establishment of NAFLD using a digital TENS device. The subsequent assessments included hepatic triglyceride, cholesterol content, serum lipid profile, and liver function testing. In this context, inflammatory biomarkers (TNF-α, IL-6) and hepatic oxidative stress (MDA, SOD, and GPx) were also assessed. To clarify the possible mechanisms behind the protective benefits of VNS, additional histological inspection and immunohistochemistry analysis of TNF-α and Caspase-3 were performed. Results: In the NAFLD-affected obese rats, VNS markedly decreased the rats’ body mass index (BMI) and abdominal circumference (AC). Liver function markers (albumin, ALT, and AST) and the serum lipid profile—which included a notable decrease in the amounts of hepatic triglycerides and cholesterol—were both markedly improved. Additionally, oxidative stress and inflammatory indicators showed a considerable decline with VNS. Notably, the liver tissues examined by histopathologists revealed that there is evidence of the protective impact of VNS on the oxidative and inflammatory states linked to HFD-induced NAFLD while maintaining the architectural and functional condition of the liver. Conclusions: Our findings suggest that VNS may represent a promising therapeutic candidate for managing NAFLD induced by obesity. It can be considered to be an effective adjuvant physiological intervention for the obese population with NAFLD to spare the liver against obesity-induced deleterious injury.https://www.mdpi.com/2227-9059/11/12/3255high-fat dietobesitynon-alcoholic fatty livervagus nerve
spellingShingle Hany A. Elkattawy
Samar Mortada Mahmoud
Ahmed El-Sayed Hassan
Ahmed Behiry
Hasnaa Ali Ebrahim
Ateya Megahed Ibrahim
Donia Elsaid Fathi Zaghamir
Mohamed El-Sherbiny
Sherein F. El-Sayed
Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats
Biomedicines
high-fat diet
obesity
non-alcoholic fatty liver
vagus nerve
title Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats
title_full Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats
title_fullStr Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats
title_full_unstemmed Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats
title_short Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats
title_sort vagal stimulation ameliorates non alcoholic fatty liver disease in rats
topic high-fat diet
obesity
non-alcoholic fatty liver
vagus nerve
url https://www.mdpi.com/2227-9059/11/12/3255
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