Duodenojejunal Bypass Plus Sleeve Gastrectomy Reduces Infiltration of Macrophages and Secretion of TNF-α in the Visceral White Adipose Tissue of Goto-Kakizaki Rats



Current studies indicate that inflammation of white adipose tissue (WAT) is a pathogenic characteristic of insulin resistance. However, the significance of visceral WAT inflammation after bariatric surgery remains unclear.


Duodenojejunal bypass plus sleeve gastrectomy (DJB-SG) was performed on Goto-Kakisaki rats. Weight, fasting blood glucose (FBG), and homeostatic model assessment of insulin resistance (HOMA-IR) in the DJB-SG group were compared to those in a sham surgery (SHAM) group every 2 weeks. The results of an oral glucose tolerance test (OGTT) and the volume of visceral adipose tissue (Visc.Fat) were compared before and 8 weeks postsurgery. Eight weeks after surgery, the rats were sacrificed and visceral WAT collected from the greater omentum. Tumor necrosis factor-α (TNF-α) and cluster of differentiation 68 (CD68) expression in the WAT were evaluated in paraffin-embedded sections by immunohistochemistry.


Compared with the SHAM group, the DJB-SG group demonstrated a significant reduction in weight, FBG, and HOMA-IR (P < 0.05), with elevation of insulin levels (P < 0.05) from 4 weeks after surgery. OGTT and the quantity of Visc.Fat were significantly reduced (P < 0.05) 8 weeks after surgery. Moreover, the expression of TNF-α and CD68 in the visceral white adipose tissue was significantly lower 8 weeks after surgery (P < 0.05).


The DJB-SG model established in Goto-Kakisaki rats achieved anticipated efficacy. Reduced TNF-α-related inflammation in visceral WAT may result in improved insulin resistance.

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  1. 1.

    Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003;289:76.

    Article  Google Scholar 

  2. 2.

    Adams TD, Davidson LE, Litwin SE, et al. Weight and metabolic outcomes 12 years after gastric bypass. N Engl J Med. 2017;377:1143–55.

    Article  Google Scholar 

  3. 3.

    Sanchez-Pernaute A et al. Proximal duodenal-ileal end-to-side bypass with sleeve gastrectomy: proposed technique. Obes Surg. 2007;17:1614–8.

    Article  Google Scholar 

  4. 4.

    Kasama K, Tagaya N, Kanehira E, et al. Laparoscopic sleeve gastrectomy with duodenojejunal bypass: technique and preliminary results. Obes Surg. 2009;19:1341–5.

    Article  Google Scholar 

  5. 5.

    Lee WJ, Lee KT, Kasama K, et al. Laparoscopic single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy (SADJB-SG): short-term result and comparison with gastric bypass. Obes Surg. 2014;24:109–13.

    Article  Google Scholar 

  6. 6.

    Navarrete SA, Leyba JL, Llopis SN. Laparoscopic sleeve gastrectomy with duodenojejunal bypass for the treatment of type 2 diabetes in non-obese patients: technique and preliminary results. Obes Surg. 2011;21:663–7.

    Article  Google Scholar 

  7. 7.

    Astiarraga B, Gastaldelli A, Muscelli E, et al. Biliopancreatic diversion in nonobese patients with type 2 diabetes: impact and mechanisms. J Clin Endocrinol Metab. 2013;98:2765–73.

    CAS  Article  Google Scholar 

  8. 8.

    Heneghan HM, Nissen S, Schauer PR. Gastrointestinal surgery for obesity and diabetes: weight loss and control of hyperglycemia. Curr Atheroscler Rep. 2012;14:579–87.

    CAS  Article  Google Scholar 

  9. 9.

    Severino A, Castagneto-Gissey L, Raffaelli M, et al. Early effect of roux-en-Y gastric bypass on insulin sensitivity and signaling. Surg Obes Relat Dis. 2016;12:42–7.

    Article  Google Scholar 

  10. 10.

    Masoodi M, Kuda O, Rossmeisl M, et al. Lipid signaling in adipose tissue: Connecting inflammation &amp; metabolism. Biochim Biophys Acta. 2015;1851:503–18.

    CAS  Article  Google Scholar 

  11. 11.

    Kanda H, Tateya S, Tamori Y, et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006;116:1494–505.

    CAS  Article  Google Scholar 

  12. 12.

    Moraes-Vieira PM, Yore MM, Dwyer PM, et al. RBP4 activates antigen-presenting cells, leading to adipose tissue inflammation and systemic insulin resistance. Cell Metab. 2014;19:512–26.

    CAS  Article  Google Scholar 

  13. 13.

    Borst SE. The role of TNF-alpha in insulin resistance. Endocrine. 2004;23:177–82.

    CAS  Article  Google Scholar 

  14. 14.

    Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244:741–9.

    Article  Google Scholar 

  15. 15.

    Hill AM, LaForgia J, Coates AM, et al. Estimating abdominal adipose tissue with DXA and anthropometry. Obesity (Silver Spring). 2007;15:504–10.

    Article  Google Scholar 

  16. 16.

    Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004;239(1):1–11.

    Article  Google Scholar 

  17. 17.

    Breen DM, Rasmussen BA, Kokorovic A, et al. Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes. Nat Med. 2012;18:950–5.

    CAS  Article  Google Scholar 

  18. 18.

    Jurowich CF, Rikkala PR, Thalheimer A, et al. Duodenal-jejunal bypass improves glycemia and decreases SGLT1-mediated glucose absorption in rats with streptozotocin-induced type 2 diabetes. Ann Surg. 2013;258:89–97.

    Article  Google Scholar 

  19. 19.

    Gavin TP, Sloan RC, Lukosius EZ, et al. Duodenal-jejunal bypass surgery does not increase skeletal muscle insulin signal transduction or glucose disposal in Goto-Kakizaki type 2 diabetic rats. Obes Surg. 2011;21:231–7.

    Article  Google Scholar 

  20. 20.

    Elffers TW et al. Body fat distribution, in particular visceral fat, is associated with cardiometabolic risk factors in obese women. PLoS One. 2017;e185403:12.

    Google Scholar 

  21. 21.

    Jablonowska-Lietz B, Wrzosek M, Wlodarczyk M, et al. New indexes of body fat distribution, visceral adiposity index, body adiposity index, waist-to-height ratio, and metabolic disturbances in the obese. Kardiol Pol. 2017;75:1185.

    Article  Google Scholar 

  22. 22.

    Lee SW, Son JY, Kim JM, et al. Body fat distribution is more predictive of all-cause mortality than overall adiposity. Diabetes Obes Metab. 2018;20:141–7.

    CAS  Article  Google Scholar 

  23. 23.

    Taniguchi A, Nakai Y, Sakai M, et al. Relationship of regional adiposity to insulin resistance and serum triglyceride levels in nonobese Japanese type 2 diabetic patients. METABOLISM. 2002;51:544–8.

    CAS  Article  Google Scholar 

  24. 24.

    Ko GTC, Tang JSF. Waist circumference and BMI cut-off based on 10-year cardiovascular risk: evidence for “central pre-obesity”. OBESITY. 2007;15:2832–9.

    Article  Google Scholar 

  25. 25.

    Wang J, Thornton JC, Russell M, et al. Asians have lower body mass index (BMI) but higher percent body fat than do whites: comparisons of anthropometric measurements. Am J Clin Nutr. 1994;60:23–8.

    CAS  Article  Google Scholar 

  26. 26.

    Baron SH. Salicylates as hypoglycemic agents. Diabetes Care. 1982;5:64–71.

    CAS  Article  Google Scholar 

  27. 27.

    Allison MA, Jensky NE, Marshall SJ, et al. Sedentary behavior and adiposity-associated inflammation: the Multi-Ethnic Study of Atherosclerosis. Am J Prev Med. 2012;42:8.

    Article  Google Scholar 

  28. 28.

    Ctoi AF et al. Metabolically healthy versus unhealthy morbidly obese: chronic inflammation, nitro-oxidative stress, and insulin resistance. Nutrients. 2018;10

  29. 29.

    Hotamisligil GS. Mechanisms of TNF-alpha-induced insulin resistance. Exp Clin Endocrinol Diabetes. 1999;107:119.

    CAS  Article  Google Scholar 

  30. 30.

    Uysal KT, Wiesbrock SM, Marino MW, et al. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389:610.

    CAS  Article  Google Scholar 

  31. 31.

    Hotamisligil GS et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–70.

    CAS  Article  Google Scholar 

  32. 32.

    Plomgaard P, Bouzakri K, Krogh-Madsen R, et al. Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation. DIABETES. 2005;54:2939–45.

    CAS  Article  Google Scholar 

  33. 33.

    Bouzakri K, Zierath JR. MAP4K4 gene silencing in human skeletal muscle prevents tumor necrosis factor-alpha-induced insulin resistance. J Biol Chem. 2007;282:7783–9.

    CAS  Article  Google Scholar 

  34. 34.

    Li J, Tang Y, Cai D. IKKbeta/NF-kappaB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes. Nat Cell Biol. 2012;14:999–1012.

    CAS  Article  Google Scholar 

  35. 35.

    van Greevenbroek MM, Schalkwijk CG, Stehouwer CD. Obesity-associated low-grade inflammation in type 2 diabetes mellitus: causes and consequences. Neth J Med. 2013;71:174.

    PubMed  Google Scholar 

  36. 36.

    Leon-Pedroza JI et al. Low-grade systemic inflammation and the development of metabolic diseases: from the molecular evidence to the clinical practice. Cir Cir. 2015;83:543–51.

    PubMed  Google Scholar 

  37. 37.

    Kelloff GJ, Sigman CC. Cancer biomarkers: selecting the right drug for the right patient. Nat Rev Drug Discov. 2012;11:201–14.

    CAS  Article  Google Scholar 

  38. 38.

    Sattar N, Gaw A, Scherbakova O, et al. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the west of Scotland coronary prevention study. Circulation. 2003;108:414–9.

    CAS  Article  Google Scholar 

  39. 39.

    Trak-Smayra V, Dargere D, Noun R, et al. Serum proteomic profiling of obese patients: correlation with liver pathology and evolution after bariatric surgery. Gut. 2009;58:825–32.

    CAS  Article  Google Scholar 

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This work was supported by the Science and Technology Planning Project of Guangzhou, China (Nos. 201508020002 and 201604020106), and the Science and Technology Planning Project of Guangdong Province, China (No. 2017ZC0324).

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Correspondence to Xiaojiang Dai or Liangping Wu.

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Conflict of Interest

Hao Yu, Zhigao Song, Hongbin Zhang, Kehong Zheng, Junfang Zhan,Jingbo Sun, Zhizhi Wang, Lucas Zellmer, Xiaojiang Dai, Wu Liangping declare that they have no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of Guangzhou General Hospital of Guangzhou Military Command’s research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

All applicable Guangzhou General Hospital of Guangzhou Military Command’s guidelines for the care and use of animals were followed.

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All animal experimental procedures involved in this study were approved by the Animal Care and Utilization Committee of Guangzhou General Hospital of Guangzhou Military Command.

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Yu, H., Song, Z., Zhang, H. et al. Duodenojejunal Bypass Plus Sleeve Gastrectomy Reduces Infiltration of Macrophages and Secretion of TNF-α in the Visceral White Adipose Tissue of Goto-Kakizaki Rats. OBES SURG 29, 1742–1750 (2019). https://doi.org/10.1007/s11695-019-03755-1

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  • DJB-SG
  • Insulin resistance
  • Inflammation
  • T2D