Morphofunctional Changes After Sleeve Gastrectomy and Very Low Calorie Diet in an Animal Model of Non-Alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease and is found in 70% of obese people. The evidence available to date suggests that bariatric surgery could be an effective treatment by reducing weight and also by improving metabolic complications in the long term. This work aimed to compare, in a diet-induced NAFLD animal model, the effect of both sleeve gastrectomy (SG) and very-low calorie diet (VLCD).
Thirty-five Wistar rats were divided into control rats (n = 7) and obese rats fed a high-fat diet (HFD). After 10 weeks, the obese rats were subdivided into four groups: HFD (n = 7), VLCD (n = 7), and rats submitted to either a sham operation (n = 7) or SG (n = 7). Both liver tissue and blood samples were processed to evaluate steatosis and NASH changes in histology (Oil Red, Sirius Red and H&E); presence of endothelial damage (CD31, Moesin/p-Moesin, Akt/p-Akt, eNOS/p-eNOS), oxidative stress (iNOS) and fibrosis (αSMA, Col1, PDGF, VEGF) proteins in liver tissue; and inflammatory (IL6, IL10, MCP-1, IL17α, TNFα), liver biochemical function, and hormonal (leptin, ghrelin, visfatin and insulin) alterations in plasma.
Both VLCD and SG improved histology, but only SG induced a significant weight loss, improved endothelial damage, and a decreased cardiovascular risk by reducing insulin resistance (IR), leptin, total cholesterol, and triglyceride levels. There were no relevant variations in the inflammatory and fibrosis markers.
Our study suggests a slight superiority of SG over VLCD by improving not only the histology but also the IR and cardiovascular risk markers related to NAFLD.
KeywordsFatty liver disease Very low calorie diet Sleeve gastrectomy Inflammation Liver fibrosis Endothelial damage Bariatric surgery animal model
Compliance with Ethical Standards
Salvador Augustin is a recipient of a Juan Rodés grant from Instituto de Salud Carlos III, Spain. The study was partially funded by grants PI12/00448 (IP: JM Balibrea), PI13/01289, and PI14/00331 from Instituto de Salud Carlos III, Spain and co-funded by European Union (ERDF/ESF, “Investing in your future”). CIBERehd is supported by Instituto de Salud Carlos III, Spain.
Conflict of Interest
Dr. Talavera-Urquijo has nothing to disclose.
Dr. Rodríguez-Navarro has nothing to disclose.
Dr. Beisani has nothing to disclose.
Dr. Salcedo-Allende has nothing to disclose.
Dr. Chakkur has nothing to disclose.
Dr. Arús-Avilés has nothing to disclose.
Dr. Cremades has nothing to disclose.
Dr. Augustin reports grants from Instituto Carlos III during the conduct of the study.
Dr. Martell reports grants from Instituto Carlos III, during the conduct of the study.
Dr. Balibrea reports grants from Instituto Carlos III, during the conduct of the study; personal fees from Johnson&Johnson (Ethicon), outside the submitted work.
- 1.World Health Organization. Obesity and overweight [Internet]. Geneva: World Health Organization; 2016. Jun [cited 2016 Oct 01] Available from: http://www.who.int/mediacentre/factsheets/fs311/en/ Google Scholar
- 2.Bonora E, Targher G. Increased risk of cardiovascular disease and chronic kidney disease in NAFLD. Nat Rev Gastroenterol Hepatol. 2012; doi: 10.1038/nrgastro.2012.79.
- 3.Association E, Association E, Easd D, et al. Clinical practice guidelines EASL—EASD—EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Clinical Practice Guidelines. J Hepatol. European Association for the Study of the Liver; 2016; Available from. 10.1016/j.jhep.2015.11.004
- 12.Chavez-Tapia Norberto C, Tellez-Avila Felix I, Barrientos-Gutierrez T, et al.. Bariatric surgery for non-alcoholic steatohepatitis in obese patients. Cochrane Database Syst Rev. 2010;(1).Google Scholar
- 13.Sasaki A, Nitta H, Otsuka K, et al. Bariatric surgery and non-alcoholic fatty liver disease: current and potential future treatments. Front Endocrinol (Lausanne). 2014;5:1–6.Google Scholar
- 14.Ph D, Johnson FK. Development of a sleeve gastrectomy weight-loss model in obese Zucker rats. NIH Public Access. 2010;157(2):567–83.Google Scholar
- 18.Leite NC, Villela-nogueira CA, Cardoso CRL, et al Non-alcoholic fatty liver disease and diabetes: from physiopathological interplay to diagnosis and treatment. 2014;20(26):8377–92.Google Scholar
- 19.Athyros VG, Tziomalos K, Katsiki N, et al. 2015 Advances in nonalcoholic fatty liver disease cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease : an update. 2015;21(22):6820–34.Google Scholar
- 24.Pasarín M, La Mura V, Gracia-Sancho J, et al. Sinusoidal endothelial dysfunction precedes inflammation and fibrosis in a model of NAFLD. PLoS One. 2012;7(4).Google Scholar
- 25.Gloy VL, Briel M, Bhatt DL, et al Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of. 2013;5934(October):1–16.Google Scholar