Authors:
,
,
,
, and
Walaa O. Obydah
walaa-obydah@live.com
https://orcid.org/0000-0003-3877-547X
Walaa O. Obydah
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt
Search for other papers by Walaa O. Obydah in
Current site
Google Scholar
PubMed
Search for other papers by Walaa O. Obydah in
Current site
Google Scholar
PubMed
Gehan A. Shaker
Gehan A. Shaker
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt
Search for other papers by Gehan A. Shaker in
Current site
Google Scholar
PubMed
Search for other papers by Gehan A. Shaker in
Current site
Google Scholar
PubMed
Shereen M. Samir
Shereen M. Samir
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt
Search for other papers by Shereen M. Samir in
Current site
Google Scholar
PubMed
Search for other papers by Shereen M. Samir in
Current site
Google Scholar
PubMed
Soheir F. El Bassiony
Soheir F. El Bassiony
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt
Search for other papers by Soheir F. El Bassiony in
Current site
Google Scholar
PubMed
Search for other papers by Soheir F. El Bassiony in
Current site
Google Scholar
PubMed
Hanaa A. Abd El Moneim
Hanaa A. Abd El Moneim
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt
Search for other papers by Hanaa A. Abd El Moneim in
Current site
Google Scholar
PubMed
Search for other papers by Hanaa A. Abd El Moneim in
Current site
Google Scholar
PubMed
Abstract
Background and aims
The prevalence of non-alcoholic fatty liver disease has been alarmingly increased with no lines of effective treatment. Vanillic acid is a naturally occurring polyphenol with promising therapeutic effects. Exercise is well known to be an effective tool against obesity and its consequences. Thus, we aim to study the effect of vanillic acid alone and along with exercise on fatty liver induced by a high-fat diet in a rat model and to investigate possible novel mechanisms involved in their action.
Methods
In this study, 40 male rats were divided equally into five groups: control (standard chow diet), HFD (high-fat diet), HFD+VA (HFD+ vanillic acid (50 mg/kg/day orally), HFD+EX (HFD+ swimming exercise 5 days/week), HFD+VA+EX (HFD+ vanillic acid+ swimming exercise) for eight weeks.
Results
Body mass, liver weight, liver enzymes, cholesterol, and triglycerides were significantly decreased in the combined VA+EX group, with marked improvement in hyperglycemia, hyperinsulinemia, and consequently HOMA-IR index compared to the HFD group. These improvements were also reflected in the pathological view. VA and swimming, either solely or in combination, markedly increased hepatic and circulating fibroblast growth factor 21. Additionally, VA and swimming increased the immunohistochemical expression of the autophagosomal marker LC3 and decreased the expression of P62, which is selectively degraded during autophagy.
Conclusions
These results suggest the hepatoprotective effect of VA and swimming exercise against fatty liver and the involvement of FGF21 and autophagy in their effect.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Perumpail BJ , Khan MA , Yoo ER , Cholankeril G , Kim D , Ahmed A . Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol 2017;23(47):8263–76.
-
2.
Ge X , Chen C , Hui X , Wang Y , Lam KS , Xu A . Fibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes. J Biol Chem 2011;286(40):34533–41.
-
3.
Berglund ED , Li CY , Bina HA , Lynes SE , Michael MD , Shanafelt AB , et al. Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity. Endocrinology 2009;150(9):4084–93.
-
4.
Badman MK , Koester A , Flier JS , Kharitonenkov A , Maratos-Flier E . Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis. Endocrinology 2009;150(11):4931–40.
-
5.
Ding WX , Li M , Yin XM . Selective taste of ethanol-induced autophagy for mitochondria and lipid droplets. Autophagy 2011;7(2):248–9.
-
6.
Yang L , Li P , Fu S , Calay ES , Hotamisligil GS . Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab 2010;11(6):467–78.
-
7.
Delaquis P , Stanich K , Toivonen P . Effect of pH on the inhibition of Listeria spp. by vanillin and vanillic acid. J Food Prot 2005;68(7):1472–6.
-
8.
Prince PS , Dhanasekar K , Rajakumar S . Preventive effects of vanillic acid on lipids, bax, bcl-2 and myocardial infarct size on isoproterenol-induced myocardial infarcted rats: a biochemical and in vitro study. Cardiovasc Toxicol 2011;11(1):58–66.
-
9.
Jung Y , Park J , Kim HL , Sim JE , Youn DH , Kang J , et al. Vanillic acid attenuates obesity via activation of the AMPK pathway and thermogenic factors in vivo and in vitro. FASEB J 2018;32(3):1388–402.
-
10.
Chang WC , Wu JS , Chen CW , Kuo PL , Chien HM , Wang YT , et al. Protective effect of vanillic acid against hyperinsulinemia, hyperglycemia and hyperlipidemia via alleviating hepatic insulin resistance and inflammation in high-fat diet (HFD)-Fed rats. Nutrients 2015;7(12):9946–59.
-
11.
Kantartzis K , Thamer C , Peter A , Machann J , Schick F , Schraml C , et al. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut 2009;58(9):1281–8.
-
12.
Palve KS , Pahkala K , Suomela E , Aatola H , Hulkkonen J , Juonala M , et al. Cardiorespiratory fitness and risk of fatty liver: the young finns study. Med Sci Sports Exerc 2017;49(9):1834–41.
-
13.
van der Windt DJ , Sud V , Zhang H , Tsung A , Huang H . The effects of physical exercise on fatty liver disease. Gene Expr 2018;18(2):89–101.
-
14.
Abdul Kadir NA , Rahmat A , Jaafar HZ . Protective effects of Tamarillo (Cyphomandra betacea) extract against high fat diet induced obesity in Sprague-Dawley rats. J Obes 2015;2015:846041.
-
15.
Andrade JM , Paraiso AF , de Oliveira MV , Martins AM , Neto JF , Guimaraes AL , et al. Resveratrol attenuates hepatic steatosis in high-fat fed mice by decreasing lipogenesis and inflammation. Nutrition 2014;30(7–8):915–9.
-
16.
Kumar S , Prahalathan P , Raja B . Antihypertensive and antioxidant potential of vanillic acid, a phenolic compound in L-NAME-induced hypertensive rats: a dose-dependence study. Redox Rep 2011;16(5):208–15.
-
17.
Stone V , Kudo KY , Marcelino TB , August PM , Matte C . Swimming exercise enhances the hippocampal antioxidant status of female Wistar rats. Redox Rep 2015;20(3):133–8.
-
18.
Trinder P . Determination of blood glucose using 4-amino phenazone as oxygen acceptor. J Clin Pathol 1969;22(2):246.
-
19.
Matthews DR , Hosker JP , Rudenski AS , Naylor BA , Treacher DF , Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28(7):412–9.
-
20.
Brunt EM , Janney CG , Di Bisceglie AM , Neuschwander-Tetri BA , Bacon BR . Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999;94(9):2467–74.
-
21.
Kanuri G , Bergheim I . In vitro and in vivo models of non-alcoholic fatty liver disease (NAFLD). Int J Mol Sci 2013;14(6):11963–80.
-
22.
Gruben N , Shiri-Sverdlov R , Koonen DP , Hofker MH . Nonalcoholic fatty liver disease: a main driver of insulin resistance or a dangerous liaison? Biochim Biophys Acta 2014;1842(11):2329–43.
-
23.
Calixto-Campos C , Carvalho TT , Hohmann MS , Pinho-Ribeiro FA , Fattori V , Manchope MF , et al. Vanillic acid inhibits inflammatory pain by inhibiting Neutrophil Recruitment, oxidative stress, Cytokine production, and NFkappaB activation in mice. J Nat Prod 2015;78(8):1799–808.
-
24.
Stanford KI , Middelbeek RJ , Townsend KL , Lee MY , Takahashi H , So K , et al. A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis. Diabetes 2015;64(6):2002–14.
-
25.
Gorgens SW , Eckardt K , Jensen J , Drevon CA , Eckel J . Exercise and regulation of adipokine and Myokine production. Prog Mol Biol Transl Sci 2015;135:313–36.
-
26.
Bostrom PA , Graham EL , Georgiadi A , Ma X . Impact of exercise on muscle and nonmuscle organs. IUBMB Life 2013;65(10):845–50.
-
27.
Zhang X , Yeung DC , Karpisek M , Stejskal D , Zhou ZG , Liu F , et al. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 2008;57(5):1246–53.
-
28.
Ejaz A , Martinez-Guino L , Goldfine AB , Ribas-Aulinas F , De Nigris V , Ribo S , et al. Dietary betaine supplementation increases Fgf21 levels to improve glucose homeostasis and reduce hepatic lipid accumulation in mice. Diabetes 2016;65(4):902–12.
-
29.
Sun Y , Xia M , Yan H , Han Y , Zhang F , Hu Z , et al. Berberine attenuates hepatic steatosis and enhances energy expenditure in mice by inducing autophagy and fibroblast growth factor 21. Br J Pharmacol 2018;175(2):374–87.
-
30.
Zeng K , Tian L , Patel R , Shao W , Song Z , Liu L , et al. Diet polyphenol curcumin Stimulates hepatic Fgf21 production and restores its sensitivity in high-fat-diet-fed male mice. Endocrinology 2017;158(2):277–92.
-
31.
Liu K , Czaja MJ . Regulation of lipid stores and metabolism by lipophagy. Cell Death Differ 2013;20(1):3–11.
-
32.
Chun SK , Lee S , Yang MJ , Leeuwenburgh C , Kim JS . Exercise-induced autophagy in fatty liver disease. Exerc Sport Sci Rev 2017;45(3):181–6.
-
33.
Ohashi T , Nakade Y , Ibusuki M , Kitano R , Yamauchi T , Kimoto S , et al. Conophylline inhibits high fat diet-induced non-alcoholic fatty liver disease in mice. PLoS One 2019;14(1):e0210068.
-
34.
Koga H , Kaushik S , Cuervo AM . Altered lipid content inhibits autophagic vesicular fusion. FASEB J 2010;24(8):3052–65.
Editor-in-Chief
László ROSIVALL (Semmelweis University, Budapest, Hungary)
Managing Editor
Anna BERHIDI (Semmelweis University, Budapest, Hungary)
Co-Editors
- Gábor SZÉNÁSI (Semmelweis University, Budapest, Hungary)
- Ákos KOLLER (Semmelweis University, Budapest, Hungary)
- Zsolt RADÁK (University of Physical Education, Budapest, Hungary)
- László LÉNÁRD (University of Pécs, Hungary)
- Zoltán UNGVÁRI (Semmelweis University, Budapest, Hungary)
Assistant Editors
- Gabriella DÖRNYEI (Semmelweis University, Budapest, Hungary)
- Zsuzsanna MIKLÓS (Semmelweis University, Budapest, Hungary)
- György NÁDASY (Semmelweis University, Budapest, Hungary)
Hungarian Editorial Board
- György BENEDEK (University of Szeged, Hungary)
- Zoltán BENYÓ (Semmelweis University, Budapest, Hungary)
- Mihály BOROS (University of Szeged, Hungary)
- László CSERNOCH (University of Debrecen, Hungary)
- Magdolna DANK (Semmelweis University, Budapest, Hungary)
- László DÉTÁRI (Eötvös Loránd University, Budapest, Hungary)
- Zoltán GIRICZ (Semmelweis University, Budapest, Hungary and Pharmahungary Group, Szeged, Hungary)
- Zoltán HANTOS (Semmelweis University, Budapest and University of Szeged, Hungary)
- Zoltán HEROLD (Semmelweis University, Budapest, Hungary)
- László HUNYADI (Semmelweis University, Budapest, Hungary)
- Gábor JANCSÓ (University of Pécs, Hungary)
- Zoltán KARÁDI (University of Pecs, Hungary)
- Miklós PALKOVITS (Semmelweis University, Budapest, Hungary)
- Gyula PAPP (University of Szeged, Hungary)
- Gábor PAVLIK (University of Physical Education, Budapest, Hungary)
- András SPÄT (Semmelweis University, Budapest, Hungary)
- Gyula SZABÓ (University of Szeged, Hungary)
- Zoltán SZELÉNYI (University of Pécs, Hungary)
- Lajos SZOLLÁR (Semmelweis University, Budapest, Hungary)
- József TOLDI (MTA-SZTE Neuroscience Research Group and University of Szeged, Hungary)
- Árpád TÓSAKI (University of Debrecen, Hungary)
International Editorial Board
- Dragan DJURIC (University of Belgrade, Serbia)
- Christopher H. FRY (University of Bristol, UK)
- Stephen E. GREENWALD (Blizard Institute, Barts and Queen Mary University of London, UK)
- Tibor HORTOBÁGYI (University of Groningen, Netherlands)
- George KUNOS (National Institutes of Health, Bethesda, USA)
- Massoud MAHMOUDIAN (Iran University of Medical Sciences, Tehran, Iran)
- Tadaaki MANO (Gifu University of Medical Science, Japan)
- Luis Gabriel NAVAR (Tulane University School of Medicine, New Orleans, USA)
- Hitoo NISHINO (Nagoya City University, Japan)
- Ole H. PETERSEN (Cardiff University, UK)
- Ulrich POHL (German Centre for Cardiovascular Research and Ludwig-Maximilians-University, Planegg, Germany)
- Andrej A. ROMANOVSKY (University of Arizona, USA)
- Anwar Ali SIDDIQUI (Aga Khan University, Karachi, Pakistan)
- Csaba SZABÓ (University of Fribourg, Switzerland)
- Eric VICAUT (Université de Paris, UMRS 942 INSERM, France)
Editorial Correspondence:
Physiology International
Semmelweis University
Faculty of Medicine, Institute of Translational Medicine
Nagyvárad tér 4, H-1089 Budapest, Hungary
Phone/Fax: +36-1-2100-100
E-mail: pi@semmelweis.hu
Indexing and Abstracting Services:
- Biological Abstracts
- BIOSIS Previews
- CAB Abstracts
- CABELLS Journalytics
- EMBASE/Excerpta Medica
- Global Health
- Index Copernicus
- Index Medicus
- Medline
- Referativnyi Zhurnal
- SCOPUS
- WoS - Science Citation Index Expanded
| 2024 | |
|---|---|
| Scopus | |
| CiteScore | |
| CiteScore rank | |
| SNIP | |
| Scimago | |
| SJR index | 0.356 |
| SJR Q rank | Q2 |
| 2023 | |
|---|---|
| Web of Science | |
| Journal Impact Factor | 2.2 |
| Rank by Impact Factor | Q3 (Physiology) |
| Journal Citation Indicator | 0.58 |
| Scopus | |
| CiteScore | 3.4 |
| CiteScore rank | Q2 (Physical Therapy, Sports Therapy and Rehabilitation) |
| SNIP | 0.508 |
| Scimago | |
| SJR index | 0.407 |
| SJR Q rank | Q2 |
| Physiology International | |
|---|---|
| Publication Model | Hybrid |
| Submission Fee | none |
| Article Processing Charge | Effective from 1st Apr 2025: 600 EUR/article |
| Printed Color Illustrations | 40 EUR (or 10 000 HUF) + VAT / piece |
| Regional discounts on country of the funding agency | World Bank Lower-middle-income economies: 50% World Bank Low-income economies: 100% |
| Further Discounts | Editorial Board / Advisory Board members: 50% Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100% |
| Subscription fee 2025 | Online subsscription: 752 EUR / 828 USD Print + online subscription: 880 EUR / 968 USD |
| Subscription Information | Online subscribers are entitled access to all back issues published by Akadémiai Kiadó for each title for the duration of the subscription, as well as Online First content for the subscribed content. |
| Purchase per Title | Individual articles are sold on the displayed price. |
| Physiology International | |
|---|---|
| Language | English |
| Size | B5 |
| Year of Foundation |
2006 (1950) |
| Volumes per Year |
1 |
| Issues per Year |
4 |
| Founder | Magyar Tudományos Akadémia |
| Founder's Address |
H-1051 Budapest, Hungary, Széchenyi István tér 9. |
| Publisher | Akadémiai Kiadó |
| Publisher's Address |
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245. |
| Responsible Publisher |
Chief Executive Officer, Akadémiai Kiadó |
| ISSN | 2498-602X (Print) |
| ISSN | 2677-0164 (Online) |
Monthly Content Usage
| Abstract Views | Full Text Views | PDF Downloads | |
|---|---|---|---|
| Nov 2024 | 89 | 0 | 0 |
| Dec 2024 | 110 | 0 | 0 |
| Jan 2025 | 101 | 0 | 0 |
| Feb 2025 | 111 | 0 | 0 |
| Mar 2025 | 158 | 0 | 0 |
| Apr 2025 | 44 | 0 | 0 |
| May 2025 | 8 | 0 | 0 |
Copyright Akadémiai Kiadó AKJournals is the trademark of Akadémiai Kiadó's journal publishing business branch.
Powered by PubFactory