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Sleeve Gastrectomy Reduces Body Weight and Improves Metabolic Profile also in Obesity-Prone Rats

Abstract

Background

Susceptibility to obesity is associated with a notable inter-individual variation. The aim of the present study was to compare the effectiveness of sleeve gastrectomy (SG) on weight loss and metabolic profile in obesity-prone (OP) rats vs animals that are non-susceptible to obesity (NSO).

Methods

Young male Wistar rats (n = 101) were put in a diet-induced obesity (DIO) programme with ad libitum access to a high-fed diet (HFD) during 12 months. Body weight and food intake were regularly registered. Thereafter, rats were ranked by final body weight to identify the obesity-prone (OP) (n = 13) and non-susceptible to obesity (NSO) (n = 14) animals. OP and NSO rats were submitted to surgical interventions (sham operation, SG and pair-fed to the amount of food eaten by sleeve-gastrectomized rats). Body weight, food intake, energy expenditure, body temperature, fat pads weight, and metabolic profiling were analysed 4 weeks after surgical or dietary interventions.

Results

SG in both OP and NSO rats decreased body weight as compared to sham and pair-fed groups (P < 0.05), mainly due to reductions in subcutaneous and perirenal fat mass (P < 0.001). Total weight loss achieved in sleeve-gastrectomized OP and NSO rats was higher than that of pair-fed ones (P < 0.05), showing that the SG effect goes beyond caloric restriction. In this regard, sleeve-gastrectomized rats exhibited significantly (P < 0.05) increased basal rectal temperature together with upregulated brown adipose tissue Ucp-1 protein expression levels. A significant (P < 0.05) improvement in insulin sensitivity was also observed in both OP and NSO animals that underwent SG as compared with pair-fed counterparts.

Conclusion

Our findings provide the first evidence that obesity-prone rats also benefit from surgery responding effectively to SG, as evidenced by the significant body weight reduction and the metabolic profile improvement.

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Abbreviations

BAT:

Brown adipose tissue

BW:

Body weight

DIO:

Diet-induced obesity

EE:

Energy expenditure

EWAT:

Epididymal white adipose tissue

FFA:

Free fatty acids

HFD:

High-fat diet

HOMA:

Homeostasis model assessment

ND:

Normal diet

OP:

Obesity-prone

OR:

Obesity-resistant

PRWAT:

Perirenal white adipose tissue

QUICKI:

Quantitative insulin sensitivity check index

RER:

Respiratory exchange ratio

RT:

Room temperature

SCWAT:

Subcutaneous white adipose tissue

TG:

Triacylglycerol

TWL:

Total weight loss

References

  1. 1.

    Frühbeck G. Obesity. Screening for the evident in obesity. Nat Rev Endocrinol. 2012;8:570–2.

    Article  PubMed  Google Scholar 

  2. 2.

    Frühbeck G, Toplak H, Woodward E. Obesity: the gateway to ill health - an EASO position statement on a rising public health, clinical and scientific challenge in Europe. Obes Facts. 2013;6(2):117–20.

    Article  PubMed  Google Scholar 

  3. 3.

    West DB, Boozer CN, Moody DL, et al. Dietary obesity in nine inbred mouse strains. Am J Physiol. 1992;262(6 Pt 2):R1025–32.

    CAS  PubMed  Google Scholar 

  4. 4.

    Speakman J, Hambly C, Mitchell S, et al. Animal models of obesity. Obes Rev. 2007;8 Suppl 1:55–61.

    Article  PubMed  Google Scholar 

  5. 5.

    Schemmel R, Mickelsen O, Gill JL. Dietary obesity in rats: body weight and body fat accretion in seven strains of rats. J Nutr. 1970;100(9):1041–8.

    CAS  PubMed  Google Scholar 

  6. 6.

    Levin BE, Sullivan AC. Glucose-induced norepinephrine levels and obesity resistance. Am J Physiol. 1987;253(3 Pt 2):R475–81.

    CAS  PubMed  Google Scholar 

  7. 7.

    Levin BE, Dunn-Meynell AA, Balkan B, et al. Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am J Physiol. 1997;273(2 Pt 2):R725–30.

    CAS  PubMed  Google Scholar 

  8. 8.

    Frühbeck G, Gómez-Ambrosi J. Control of body weight: a physiologic and transgenic perspective. Diabetologia. 2003;46(2):143–72.

    PubMed  Google Scholar 

  9. 9.

    Levin BE. Developmental gene x environment interactions affecting systems regulating energy homeostasis and obesity. Front Neuroendocrinol. 2010;31(3):270–83.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Lauterio TJ, Bond JP, Ulman EA. Development and characterization of a purified diet to identify obesity-susceptible and resistant rat populations. J Nutr. 1994;124(11):2172–8.

    CAS  PubMed  Google Scholar 

  11. 11.

    Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724–37.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Sjöström L. Review of the key results from the swedish obese subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273(3):219–34.

    Article  PubMed  Google Scholar 

  13. 13.

    Frühbeck G. Bariatric and metabolic surgery: a shift in eligibility and success criteria. Nat Rev Endocrinol. 2015;11(8):465–77.

    Article  PubMed  Google Scholar 

  14. 14.

    Fried M, Yumuk V, Oppert JM, et al. Interdisciplinary European guidelines on metabolic and bariatric surgery. Obes Facts. 2013;6(5):449–68.

    Article  PubMed  Google Scholar 

  15. 15.

    Fried M, Yumuk V, Oppert JM, et al. Interdisciplinary European guidelines on metabolic and bariatric surgery. Obes Surg. 2014;24(1):42–55.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Gluck B, Movitz B, Jansma S, et al. Laparoscopic sleeve gastrectomy is a safe and effective bariatric procedure for the lower BMI (35.0-43.0 kg/m2) population. Obes Surg. 2011;21(8):1168–71.

    Article  PubMed  Google Scholar 

  17. 17.

    Gagner M, Deitel M, Erickson AL, et al. Survey on laparoscopic sleeve gastrectomy (LSG) at the fourth international consensus summit on sleeve gastrectomy. Obes Surg. 2013;23(12):2013–7.

    Article  PubMed  Google Scholar 

  18. 18.

    Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013;23(4):427–36.

    Article  PubMed  Google Scholar 

  19. 19.

    Rosenthal RJ, Diaz AA, Arvidsson D, et al. International sleeve gastrectomy expert panel consensus statement: best practice guidelines based on experience of >12,000 cases. Surg Obes Relat Dis. 2012;8(1):8–19.

    Article  PubMed  Google Scholar 

  20. 20.

    Eid GM, Brethauer S, Mattar SG, et al. Laparoscopic sleeve gastrectomy for super obese patients: forty-eight percent excess weight loss after 6 to 8 years with 93% follow-up. Ann Surg. 2012;256(2):262–5.

    Article  PubMed  Google Scholar 

  21. 21.

    Pereferrer FS, Gonzalez MH, Rovira AF, et al. Influence of sleeve gastrectomy on several experimental models of obesity: metabolic and hormonal implications. Obes Surg. 2008;18(1):97–108.

    Article  PubMed  Google Scholar 

  22. 22.

    Valentí V, Martín M, Ramírez B, et al. Sleeve gastrectomy induces weight loss in diet-induced obese rats even if high-fat feeding is continued. Obes Surg. 2011;21(9):1438–43.

    Article  PubMed  Google Scholar 

  23. 23.

    Méndez-Giménez L, Becerril S, Moncada R, et al. Sleeve gastrectomy reduces hepatic steatosis by improving the coordinated regulation of aquaglyceroporins in adipose tissue and liver in obese rats. Obes Surg. 2015;25(9):1723–34.

    Article  PubMed  Google Scholar 

  24. 24.

    Rodríguez A, Becerril S, Valentí V, et al. Short-term effects of sleeve gastrectomy and caloric restriction on blood pressure in diet-induced obese rats. Obes Surg. 2012;22(9):1481–90.

    Article  PubMed  Google Scholar 

  25. 25.

    Rodríguez A, Becerril S, Valentí V, et al. Sleeve gastrectomy reduces blood pressure in obese (fa/fa) Zucker rats. Obes Surg. 2012;22(2):309–15.

    Article  PubMed  Google Scholar 

  26. 26.

    Martín M, Burrell MA, Gómez-Ambrosi J, et al. Short- and long-term changes in gastric morphology and histopathology following sleeve gastrectomy in diet-induced obese rats. Obes Surg. 2012;22(4):634–40.

    Article  PubMed  Google Scholar 

  27. 27.

    Frühbeck G, Alonso R, Marzo F, et al. A modified method for the indirect quantitative analysis of phytate in foodstuffs. Anal Biochem. 1995;225:206–12.

    Article  PubMed  Google Scholar 

  28. 28.

    Becerril S, Rodríguez A, Catalán V, et al. Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function. PLoS ONE. 2010;5(6):e10962.

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Lancha A, Moncada R, Valentí V, et al. Effect of sleeve gastrectomy on osteopontin circulating levels and expression in adipose tissue and liver in rats. Obes Surg. 2014;24(10):1702--8.

  30. 30.

    Muruzábal FJ, Frühbeck G, Gómez-Ambrosi J, et al. Immunocytochemical detection of leptin in non-mammalian vertebrate stomach. Gen Comp Endocrinol. 2002;128(2):149–52.

    Article  PubMed  Google Scholar 

  31. 31.

    Rodríguez A, Catalán V, Becerril S, et al. Impaired adiponectin-AMPK signalling in insulin-sensitive tissues of hypertensive rats. Life Sci. 2008;83(15-16):540–9.

    Article  PubMed  Google Scholar 

  32. 32.

    Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122(3):248–56 e5.

    Article  PubMed  Google Scholar 

  33. 33.

    Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577–85.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Nguyen NT, Nguyen B, Gebhart A, et al. Changes in the makeup of bariatric surgery: a national increase in use of laparoscopic sleeve gastrectomy. J Am Coll Surg. 2013;216(2):252–7.

    Article  PubMed  Google Scholar 

  35. 35.

    Frühbeck G, Diez Caballero A, Gil MJ. Fundus functionality and ghrelin concentrations after bariatric surgery. N Engl J Med. 2004;350:308–9.

    Article  PubMed  Google Scholar 

  36. 36.

    Bohdjalian A, Langer FB, Shakeri-Leidenmuhler S, et al. Sleeve gastrectomy as sole and definitive bariatric procedure: 5-year results for weight loss and ghrelin. Obes Surg. 2010;20(5):535–40.

    Article  PubMed  Google Scholar 

  37. 37.

    Frühbeck G, Gómez Ambrosi J, Salvador J. Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes. FASEB J. 2001;15(2):333–40.

    Article  PubMed  Google Scholar 

  38. 38.

    Rodríguez A, Gómez-Ambrosi J, Catalán V, et al. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Int J Obes. 2009;33(5):541–52.

    Article  Google Scholar 

  39. 39.

    Rodriguez A. Novel molecular aspects of ghrelin and leptin in the control of adipobiology and the cardiovascular system. Obes Facts. 2014;7(2):82–95.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Frühbeck G, Gómez AJ. Rationale for the existence of additional adipostatic hormones. FASEB J. 2001;15(11):1996–2006.

    Article  PubMed  Google Scholar 

  41. 41.

    Bueter M, Löwenstein C, Olbers T, et al. Gastric bypass increases energy expenditure in rats. Gastroenterology. 2010;138(5):1845–53.

    Article  PubMed  Google Scholar 

  42. 42.

    Becerril S, Gómez-Ambrosi J, Martin M, et al. Role of PRDM16 in the activation of brown fat programming. Relevance to the development of obesity. Histol Histopathol. 2013;28(11):1411–25.

    CAS  PubMed  Google Scholar 

  43. 43.

    Saeidi N, Nestoridi E, Kucharczyk J, et al. Sleeve gastrectomy and roux-en-Y gastric bypass exhibit differential effects on food preferences, nutrient absorption and energy expenditure in obese rats. Int J Obes (Lond). 2012;36(11):1396–402.

    CAS  Article  Google Scholar 

  44. 44.

    Baraboi ED, Li W, Labbe SM, et al. Metabolic changes induced by the biliopancreatic diversion in diet-induced obesity in male rats: the contributions of sleeve gastrectomy and duodenal switch. Endocrinology. 2015;156(4):1316–29.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Das SK, Roberts SB, McCrory MA, et al. Long-term changes in energy expenditure and body composition after massive weight loss induced by gastric bypass surgery. Am J Clin Nutr. 2003;78(1):22–30.

    CAS  PubMed  Google Scholar 

  46. 46.

    Werling M, Olbers T, Fandriks L, et al. Increased postprandial energy expenditure may explain superior long term weight loss after Roux-en-Y gastric bypass compared to vertical banded gastroplasty. PLoS ONE. 2013;8(4):e60280.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Chambers AP, Jessen L, Ryan KK, et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology. 2011;141(3):950–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Kadera BE, Portenier DD, Yurcisin BM, et al. Evidence for a metabolic mechanism in the improvement of type 2 diabetes after sleeve gastrectomy in a rodent model. Surg Obes Relat Dis. 2013;9(3):447–52.

    Article  PubMed  Google Scholar 

  49. 49.

    Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17):1567–76.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes--3-year outcomes. N Engl J Med. 2014;370(21):2002–13.

    Article  PubMed  Google Scholar 

  51. 51.

    Lancha A, Moncada R, Valentí V, et al. Comparative effects of gastric bypass and sleeve gastrectomy on plasma osteopontin concentrations in humans. Surg Endosc. 2014;28(8):2412–20.

    Article  PubMed  Google Scholar 

  52. 52.

    Hall KD. Modeling metabolic adaptations and energy regulation in humans. Annu Rev Nutr. 2012;32:35–54.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Warden CH, Fisler JS. Comparisons of diets used in animal models of high-fat feeding. Cell Metab. 2008;7(4):277.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Stanhope KL, Schwarz JM, Havel PJ. Adverse metabolic effects of dietary fructose: results from the recent epidemiological, clinical, and mechanistic studies. Curr Opin Lipidol. 2013;24(3):198–206.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We gratefully acknowledge the valuable collaboration of all the staff of the breeding house of the University of Navarra.

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Correspondence to Gema Frühbeck.

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Conflict of Interest

R.M., S.B., A.R., L.M.-G., B.R., V.C., J.G.-A., M.J.G., S.F., J.A.-C., V.V. and G.F. declare that they have no conflict of interest.

This article does not contain any studies with human participants.

Funding

This work was supported by grants from the Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS PI12/00515), from the Department of Health (48/2011 and 58/2011) of the Gobierno de Navarra and from the CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain.

Additional information

Rafael Moncada and Sara Becerril contributed equally to this work.

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Moncada, R., Becerril, S., Rodríguez, A. et al. Sleeve Gastrectomy Reduces Body Weight and Improves Metabolic Profile also in Obesity-Prone Rats. OBES SURG 26, 1537–1548 (2016). https://doi.org/10.1007/s11695-015-1915-0

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Keywords

  • Susceptibility
  • Obesity phenotypes
  • Obesity-prone
  • Diet-induced obesity
  • Sleeve gastrectomy