Morphofunctional Changes After Sleeve Gastrectomy and Very Low Calorie Diet in an Animal Model of Non-Alcoholic Fatty Liver Disease

  • Eider Talavera-Urquijo
  • Sarai Rodríguez-Navarro
  • Marc Beisani
  • Maria Teresa Salcedo-Allende
  • Aisha Chakkur
  • Marc Arús-Avilés
  • Manel Cremades
  • Salvador Augustin
  • María Martell
  • José M. Balibrea
Original Contributions

Abstract

Background

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).

Methods

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.

Results

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.

Conclusion

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.

Keywords

Fatty liver disease Very low calorie diet Sleeve gastrectomy Inflammation Liver fibrosis Endothelial damage Bariatric surgery animal model 

References

  1. 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. 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. 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
  4. 4.
    Fotbolcu H, Zorlu E. Nonalcoholic fatty liver disease as a multi-systemic disease. World J Gastroenterol. 2016 Apr 28 [cited 2016 May 3];22(16):4079–90.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Popov VB, Lim JK. Treatment of nonalcoholic fatty liver disease: the role of medical, surgical, and endoscopic weight loss. J Clin Transl Hepatol. 2015 Sep 28 [cited 2016 May 8];3(3):230–8.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263–73.CrossRefPubMedGoogle Scholar
  7. 7.
    Radwan MM, Radwan BM, Nandipati KC, et al. Immunological and molecular basis of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease. Expert Rev Clin Immunol. 2013;9(8):727–38.CrossRefPubMedGoogle Scholar
  8. 8.
    Lewis MC, Phillips ML, Slavotinek JP, et al. Change in liver size and fat content after treatment with Optifast® very low calorie diet. Obes Surg. 2006;16(6):697–701.CrossRefPubMedGoogle Scholar
  9. 9.
    Shah K, Stufflebam A, Hilton TN, et al. Diet and exercise interventions reduce intrahepatic fat content and improve insulin sensitivity in obese older adults. Obesity (Silver Spring). 2009;17:2162–8. doi:10.1038/oby.2009.126.CrossRefGoogle Scholar
  10. 10.
    Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol. 2012;56(1):255–266 Available from:. doi:10.1016/j.jhep.2011.06.010.CrossRefPubMedGoogle Scholar
  11. 11.
    Hernandez-rodas MC, Valenzuela R, Videla LA. Relevant aspects of nutritional and dietary interventions in non-alcoholic fatty liver disease. Int J Mol Sci. 2015;16:25168–98. doi:10.3390/ijms161025168.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 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. 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. 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
  15. 15.
    Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.CrossRefPubMedGoogle Scholar
  16. 16.
    Dyson JK, Anstee QM, McPherson S. Non-alcoholic fatty liver disease: a practical approach to diagnosis and staging. Frontline Gastroenterol. 2014;5(3):211–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Bedossa P, Poitou C, Veyrie N, et al. Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients. Hepatology. 2012;56(5):1751–9.CrossRefPubMedGoogle Scholar
  18. 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. 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
  20. 20.
    Zhang L, Song H, Ge Y, et al. Temporal relationship between diet-induced steatosis and onset of insulin/leptin resistance in male Wistar rats. PLoS One. 2015 Jan [cited 2016 Apr 16];10(2):e0117008.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Giby VG, Ajith TA. Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease. World J Hepatol. 2014;6(8):570–9.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Fuentes T, Ara I, Guadalupe-Grau A, et al. Leptin receptor 170 kDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance. Exp Physiol. 2010;95(1):160–71.CrossRefPubMedGoogle Scholar
  23. 23.
    Polimeni L, Del Ben M, Baratta F, et al. Oxidative stress: new insights on the association of non-alcoholic fatty liver disease and atherosclerosis. World J Hepatol. 2015;7(10):1325–36.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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. 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

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Eider Talavera-Urquijo
    • 1
  • Sarai Rodríguez-Navarro
    • 2
  • Marc Beisani
    • 1
  • Maria Teresa Salcedo-Allende
    • 3
  • Aisha Chakkur
    • 2
  • Marc Arús-Avilés
    • 2
  • Manel Cremades
    • 4
  • Salvador Augustin
    • 2
    • 5
  • María Martell
    • 2
    • 5
  • José M. Balibrea
    • 1
    • 6
    • 7
  1. 1.Department of General and Digestive SurgeryVall d’Hebron University HospitalBarcelonaSpain
  2. 2.Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Institut de Recerca Vall d’Hebron (VHIR)Universitat Autònoma de BarcelonaBarcelonaSpain
  3. 3.Human Pathology DepartmentVall d’Hebron University HospitalBarcelonaSpain
  4. 4.Department of General and Digestive SurgeryGermans Trias i Pujol University HospitalBarcelonaSpain
  5. 5.Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos IIIMadridSpain
  6. 6.Metabolic and Bariatric Surgery Unit, EAC-BS Center of ExcellenceVall d’Hebron University HospitalBarcelonaSpain
  7. 7.Department of SurgeryUniversitat Autònoma de BarcelonaBarcelonaSpain

Personalised recommendations