Skip to main content

Advertisement

Log in

Inflammation of Mesenteric Adipose Tissue Correlates with Intestinal Injury and Disease Severity in Rats with Severe Acute Pancreatitis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Visceral adipose tissue (VAT) is related to SAP prognosis. As a depot of VAT, mesenteric adipose tissue (MAT) resides between pancreas and gut, which might affect SAP and the secondary intestinal injury.

Aims

To investigate the changes of MAT in SAP.

Methods

24 SD rats were randomly divided into four groups. 18 rats in SAP group were euthanized in time gradients (6 h, 24 h, and 48 h after modeling) and the others in control group. Blood samples and tissues of pancreas, gut, and MAT were taken for analysis.

Results

Compared to the control group, SAP rats appeared MAT inflammation, presenting higher mRNA expression of TNF-α and IL-6 and lower IL-10, and histological changes after 6 h of modeling, which became worse over time. Flow cytometry showed that B lymphocytes increased in MAT after 24 h of SAP modeling and lasted up to 48 h, earlier than the changes of T lymphocytes and macrophages. The intestinal barrier integrity was damaged after 6 h of modeling, presenting lower mRNA and protein expression of ZO-1 and occludin, higher serum levels of LPS and DAO, with pathological changes, which gradually aggravated after 24 h and 48 h. SAP rats had higher serum levels of inflammatory indicators and revealed histological inflammation of pancreas, the severity of which increased with the passage of modeling time.

Conclusion

MAT appeared inflammation in early-stage SAP, and became worse over time, with the same trend as the intestinal barrier injury and the severity of pancreatitis. B lymphocytes infiltrated early in MAT, which might promote the MAT inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Frossard J, Steer M, Pastor C. Acute pancreatitis. Lancet. 2008;371:143–152.

    Article  PubMed  Google Scholar 

  2. Afghani E, Pandol S, Shimosegawa T et al. Acute Pancreatitis-Progress and Challenges: A Report on an International Symposium. Pancreas. 2015;44:1195–1210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Fritz S, Hackert T, Hartwig W et al. Bacterial translocation and infected pancreatic necrosis in acute necrotizing pancreatitis derives from small bowel rather than from colon. Am J Surg. 2010;200:111–117.

    Article  PubMed  Google Scholar 

  4. Kuan L, Dennison A, Garcea G. Association of visceral adipose tissue on the incidence and severity of acute pancreatitis: a systematic review. Pancreatology. 2020;20:1056–1061.

    Article  PubMed  Google Scholar 

  5. Bukulmez A, Gokaslan C, Oflu A. Increase in visceral adipose tissue and subcutaneous adipose tissue thickness in children with acute pancreatitis. A case-control study. Arch Pediatr. 2021;28:29–32.

    Article  CAS  PubMed  Google Scholar 

  6. Mao R, Kurada S, Gordon I et al. The mesenteric fat and intestinal muscle interface: creeping fat influencing stricture formation in Crohn’s disease. Inflamm Bowel Dis. 2019;25:421–426.

    Article  PubMed  Google Scholar 

  7. Gea-Sorlí S, Laia B, Daniel C et al. Differences in the Inflammatory Response Induced by Acute Pancreatitis in Different White Adipose Tissue Sites in the Rat. Plos One 2012;7:e41933.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Li Y, Zhu W, Zuo L et al. The role of the mesentery in Crohn’s Disease: The contributions of nerves, vessels, lymphatics, and rat to the pathogenesis and disease course. Inflamm Bowel Dis. 2016;22:1483–1495.

    Article  PubMed  Google Scholar 

  9. Wu Z, Tan J, Chi Y et al. Mesenteric adipose tissue contributes to intestinal barrier integrity and protects against nonalcoholic fatty liver disease in mice. Am J Physiol Gastrointest Liver Physiol. 2018;15:G659-670.

    Article  Google Scholar 

  10. Schmidt J, Rattner D, Lewandrowski K et al. A better model of acute pancreatitis for evaluating therapy. Ann Surg. 1992;215:44–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chiu C, Scott H, Gurd F. Intestinal mucosal lesion in low-flow states. II. The protective effect of intraluminal glucose as energy substrate. Archiv Surg. 1970;101:484–488.

    Article  CAS  Google Scholar 

  12. Besselink M, Van Santvoort H, Renooij W et al. Intestinal barrier dysfunction in a randomized trial of a specific probiotic composition in acute pancreatitis. Ann Surg. 2009;250:712–719.

    Article  PubMed  Google Scholar 

  13. Shen Q, Xu G, Shen M. Effect of early enteral nutrition on endotoxin in serum and intestinal permeability in patients with severe acute pancreatitis. Eur Rev Med Pharmacol Sci. 2017;21:2764–2768.

    PubMed  Google Scholar 

  14. O’Leary D, O’Neill D, Mclaughlin P et al. Effects of Abdominal Fat Distribution Parameters on Severity of Acute Pancreatitis. World Journal of Surgery. 2012;36:1679–1685.

    Article  CAS  PubMed  Google Scholar 

  15. Caesar R, Manieri M, Kelder T et al. A combined transcriptomics and lipidomics analysis of subcutaneous, epididymal and mesenteric adipose tissue reveals marked functional differences. PLoS ONE. 2010;5:e11525.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cohen C, Shea A, Heffron C et al. Intraabdominal fat depots represent distinct immunomodulatory microenvironments: a murine model. PLoS ONE. 2013;8:e66477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wueest S, Yang X, Liu J et al. Inverse regulation of basal lipolysis in perigonadal and mesenteric fat depots in mice. Am J Physiol Endocrinol Metab. 2012;302:E153–E160.

    Article  CAS  PubMed  Google Scholar 

  18. Ko G, Liu K, So W et al. Cutoff values for central obesity in Chinese based on mesenteric fat thickness. Clin Nutr. 2009;28:679–683.

    Article  PubMed  Google Scholar 

  19. Catalano K, Stefanovski D, Bergman R. Critical role of the mesenteric depot versus other intra-abdominal adipose depots in the development of insulin resistance in young rats. Diabetes. 2010;59:1416–1423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Navina S, Acharya C, Delany J et al. Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity. Sci Transl Med 2011;3:107–110.

    Article  Google Scholar 

  21. Durgampudi C, Noel P, Patel K et al. Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation. Am J Pathol. 2014;184:1773–1784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lin T, Zhang Y, Wang Y et al. NAFLD aggravates acute pancreatitis through bacterial translocation and cholesterol metabolic dysregulation in the liver and pancreas in mice. Hepatobiliary Pancreat Dis Int 2022;S1499–3872(22):00180–00181.

    Google Scholar 

  23. Brestoff J, Artis D. Immune regulation of metabolic homeostasis in health and disease. Cell. 2015;161:146–160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Beek L, Klinken J, Pronk A et al. The limited storage capacity of gonadal adipose tissue directs the development of metabolic disorders in male C57Bl/6J mice. Diabetologia. 2015;58:1601–1609.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Winer D, Winer S, Shen L et al. B lymphocytes promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011;17:610–617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ying W, Wollam J, Ofrecio J et al. Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling. J Clin Invest. 2017;127:1019–1030.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Defuria J, Belkina A, Jaqannathan-Bogdan M et al. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci USA 2013;110:5133–5138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wu Z, Xu J, Tan J et al. Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non-alcoholic fatty liver disease mice. J Cell Mol Med. 2019;23:3375–3385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank Zhe Wu for the assistance of research design and analysis. We thank Shizhong Yang for the clinical support.

Funding

This study was supported by the Youth Fund of Beijing Tsinghua Changgung Hospital (12022C1004) and Tsinghua Precision Medicine Foundation (10001020127).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xuan Jiang.

Ethics declarations

Competing interest

All authors declare no competing interests.

Ethical approval

All protocols were approved by the Beijing Tsinghua Changgung Hospital Ethics Committee (22271-4-01).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, Q., Liu, J., Zhou, Z. et al. Inflammation of Mesenteric Adipose Tissue Correlates with Intestinal Injury and Disease Severity in Rats with Severe Acute Pancreatitis. Dig Dis Sci 68, 2474–2481 (2023). https://doi.org/10.1007/s10620-023-07846-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-023-07846-z

Keywords

Navigation