Acute Pancreatitis in Obesity: Adipokines and Dietary Fish Oil



Acute pancreatitis is a substantial clinical problem accounting for 240,000 hospital admissions yearly in the United States. Obesity is epidemic and is clearly an independent risk factor for increased severity of acute pancreatitis (AP). Adipose tissue is an endocrine organ that secretes a variety of metabolically active substances termed adipokines. However, the role of adipokines in modulating acute pancreatitis severity remains incompletely understood. Dietary fish oil is rich in omega-3 free fatty acids and attenuates adipose tissue-induced inflammation. Therefore, we hypothesized that feeding obese mice diets rich in fish oil would alter the adipokine milieu and attenuate the severity of pancreatitis.


Lean (C57BL/6 J) and obese (LepDb) mice were fed either a soybean oil- or fish oil-rich diet for 4 weeks. AP was induced by six hourly intraperitoneal injections of cerulein (50 μg/kg). Serum adipokine levels were measured, and pancreatitis severity was assessed histologically and by measuring pancreatic concentrations of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), myleoperoxidase (MPO), and monocyte chemoattractant protein-1 (MCP-1).


Obese mice developed more severe pancreatitis than lean mice. Fish oil significantly decreased serum leptin (lean and obese) and increased serum adiponectin (lean only). Fish oil did not alter the baseline pancreatic inflammatory milieu, nor did it change histologic or biochemical pancreatitis severity.


These data demonstrate that a diet rich in fish oil altered the adipokine milieu in lean and congenitally obese mice; however, fish oil did not improve pancreatitis severity induced with cerulein hyperstimulation.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA. 2006;295:1549–1555.

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Mokdad AH, Bowman BA, Ford ES, Vinicor F, Marks JS, Koplan JP. The continuing epidemics of obesity and diabetes in the United States. JAMA. 2001;286:1195–1200.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Tsochatzis E, Papatheodoridis GV, Archimandritis AJ. The evolving role of leptin and adiponectin in chronic liver diseases. Am J Gastroenterol. 2006;101:2629–2640.

    PubMed  CAS  Google Scholar 

  4. 4.

    Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003;23:85–89.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Zyromski NJ, Mathur A, Gowda GA, et al. NMR spectroscopy based metabolomics of the fatty pancreas: implicating fat in pancreatic pathology. Pancreatology. 2009;9:410–419.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Mathur A, Marine M, Lu D, et al. Nonalcoholic fatty pancreas disease. HPB. 2007;9:312–318.

    PubMed  Article  Google Scholar 

  7. 7.

    Fagenholz PJ, Fernández-del Castillo C, Harris NS, Pelletier AJ, Camargo CA Jr. Direct medical costs of acute pancreatitis hospitalizations in the United States. Pancreas. 2007;35:302–307.

    PubMed  Article  Google Scholar 

  8. 8.

    Uhl W, Warshaw A, Imrie C, et al. IAP guidelines for the surgical management of acute pancreatitis. Pancreatology. 2002;2:565–573.

    PubMed  Article  Google Scholar 

  9. 9.

    Howard TJ, Patel JB, Zyromski N, et al. Declining morbidity and mortality rates in the surgical management of pancreatic necrosis. J Gastrointest Surg. 2007;11:43–49.

    PubMed  Article  Google Scholar 

  10. 10.

    Suazo-Baráhona J, Carmona-Sánchez R, Robles-Díaz G, et al. Obesity: A risk factor for severe acute biliary and alcoholic pancreatitis. Am J Gastroenterol. 1998;93:1324–1328.

    PubMed  Google Scholar 

  11. 11.

    Papachristou GI, Papachristou DJ, Avula H, Slivka A, Whitcomb DC. Obesity increases the severity of acute pancreatitis: performance of APACHE-O score and correlation with the inflammatory response. Pancreatology. 2006;6:279–285.

    PubMed  Article  Google Scholar 

  12. 12.

    Martínez J, Johnson CD, Sánchez-Payá J, de Madaria E, Robles-Díaz G, Pérez-Mateo M. Obesity is a definitive risk factor of severity and mortality in acute pancreatitis: An updated meta-analysis. Pancreatology. 2006;6:206–209.

    PubMed  Article  Google Scholar 

  13. 13.

    Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005;115:911–919.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Fantuzzi G, Faggioni R. Faggioni. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol. 2000;68:437–446.

    PubMed  CAS  Google Scholar 

  15. 15.

    Peake PW, Kriketos AD, Campbell LV, Shen Y, Charlesworth JA. The metabolism of isoforms of human adiponectin: Studies in human subjects and in experimental animals. Eur J Endocrinol. 2005;153:409–417.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissue-derived cytokines: In vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab. 2003;285:527–533.

    Google Scholar 

  17. 17.

    Zyromski NJ, Mathur A, Yancey K, et al. A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2008;295:G552–G558.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Pitt HA. Hepato-pancreato-biliary fat: the good, the bad and the ugly. HPB. 2007;9:92–97.

    PubMed  Article  Google Scholar 

  19. 19.

    Fernandez-Real JM, Broch M, Vendrell J, Ricard W. Insulin resistance, inflammation, and serum fatty acid composition. Diabetes Care. 2003;26:1362–1368.

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Chaudhary A, Mishra A, Sethi S. Oxidized omega-3 fatty acids inhibit pro-inflammatory responses in glomerular endothelial cells. Nephron Exp Nephrol. 2004;97:e136–e145.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Poirier H, Shapiro JS, Kim RJ, Lazar MA. Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue. Diabetes. 2006;55:1634–1641.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Harvey KA, Arnold T, Rasool T, Antalis C, Miller SJ. Siddiqui RA.Trans-fatty acids induce pro-inflammatory responses and endothelial cell dysfunction. Br J Nutr. 2008;99:723–731.

    PubMed  CAS  Google Scholar 

  23. 23.

    Kromhout D, Bosschieter EB, de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med. 1985;312:1205–1209.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Wang C, Harris WS, Chung M, et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: A systematic review. Am J Clin Nutr. 2006;84:5–17.

    PubMed  CAS  Google Scholar 

  25. 25.

    Kennedy A, Martinez K, Chuang C, LaPoint K, McIntosh M. Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: Mechanisms of action and implications. J Nutr. 2009;39:1–4.

    Google Scholar 

  26. 26.

    Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn’s disease. N Engl J Med. 1996;334:1557–1560.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Endres S, Lorenz R, Loeschke K. Lipid treatment of inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 1999;2:117–120.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Drevon CA. Fatty acids and expression of adipokines. Biochim Biophys Acta. 2005;1740:287–292.

    PubMed  CAS  Google Scholar 

  29. 29.

    White PJ, Marette A. Is omega-3 key to unlocking inflammation is obesity. Diabetologia. 2006;49:1999–2001.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Higuchi T, Shirai N, Saito M, Suzuki H, Kagawa Y. Levels of plasma insulin, leptin and adiponectin, and activities of key enzymes in carbohydrate metabolism in skeletal muscle and liver in fasted ICR mice fed dietary n-3 polyunsaturated fatty acids. J Nutr Biochem. 2008;19:577–586.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Rongione AJ, Kusske AM, Kwan K, Ashley SW, Reber HA, McFadden DW. Interleukin 10 reduces the severity of acute pancreatitis in rats. Gastroenterology. 1997;112:960–967.

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Sutherland JP, McKinley B, Eckel RH. The metabolic syndrome and inflammation. Metab Syndr Relat Disord. 2004;2:82–104.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Karmiris K, Koutroubakis IE, Xidakis C, Polychronaki M, Voudouri T, Kouroumalis EA. Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease. Inflamm Bowel Dis. 2006;12:100–105.

    PubMed  Article  Google Scholar 

  34. 34.

    Toussirot E, Streit G, Wendling D. The contribution of adipose tissue and adipokines to inflammation in joint diseases. Curr Med Chem. 2007;14:1095–1100.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Fujita K, Maeda N, Sonoda M, et al. Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPAR-alpha. Arterioscler Thromb Vasc Biol. 2008;28:863–870.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Segersvärd R, Tsai JA, Herrington MK, Wang F. Obesity alters cytokine gene expression and promotes liver injury in rats with acute pancreatitis. Obesity. 2008;16:23–28.

    PubMed  Article  Google Scholar 

  37. 37.

    Segersvärd R, Sylván M, Herrington M, Larsson J, Permert J. Obesity increases the severity of acute experimental pancreatitis in the rat. Scand J Gastroenterol. 2001;36:658–663.

    PubMed  Article  Google Scholar 

  38. 38.

    Zyromski NJ, Mathur A, Pitt HA, et al. Cannabinoid receptor-1 blockade attenuates acute pancreatitis in obesity by an adiponectin mediated mechanism. J Gastrointest Surg. 2009;13:831–838.

    PubMed  Article  Google Scholar 

  39. 39.

    Higuchi T, Shirai N, Saito M, Suzuki H, Kagawa Y. Levels of plasma insulin, leptin and adiponectin, and activities of key enzymes in carbohydrate metabolism in skeletal muscle and liver in fasted ICR mice fed dietary n-3 polyunsaturated fatty acids. J Nutr Biochem. 2008;19:577–586.

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Tsitouras PD, Gucciardo F, Salbe AD, Heward C, Harman SM. High omega-3 fat intake improves insulin sensitivity and reduces CRP and IL-6, but does not affect other endocrine axes in healthy older adults. Horm Metab Res. 2008;40:199–205.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Bueno AA, Oyama LM, de Olivera C, et al. Effects of different fatty acids anf dietary lipids on adiponectin gene expression in 3T3–L1 cells and C57Bl/6 J mice adipose tissue. Pflugers Arch. 2008;455:701–709.

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Neschen S, morino K, Rossbacher JC, et al. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes. 2006;55:924–928.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Kratz M, Swarbrick MM, Callahan HS, Matthys CC, Havel PJ, Weigle DS. Effect of dietary n-3 polyunsaturated fatty acids on plasma total and high-molecular-weight adiponectin concentrations in overweight to moderately obese men and women. Am J Clin Nutr. 2008;87:347–353.

    PubMed  CAS  Google Scholar 

  44. 44.

    Kesavalu L, Bakthavatchalu V, Rahman MM, et al. Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis-induced experimental periodontal disease. Oral Microbiol Immunol. 2007;22:232–239.

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Yasukawa H, Ohishi M, Mori H, et al. IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat Immunol. 2003;4:551–556.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Aderka D, Le JM, Vilcek J. IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. J Immunol. 1989;143:3517–3523.

    PubMed  CAS  Google Scholar 

  47. 47.

    Xing Z, Gauldie J, Cox G, et al. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest. 1998;101:311–320.

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Sharif S, Broman M, Babcock T, et al. A priori dietary omega-3 lipid supplementation results in local pancreatic macrophage and pulmonary inflammatory response attenuation in a model of experimental acute edematous pancreatitis (AEP). J Parenter Enteral Nutr. 2006;30:271–276.

    Article  CAS  Google Scholar 

  49. 49.

    Foitzik T, Eibl G, Schneider P, Wenger FA, Jacobi CA, Buhr HJ. Omega-3 fatty acids supplementation increases anti-inflammatory cytokine and attenuates systemic disease sequelae in experimental pancreatitis. J Parenter Enteral Nutr. 2002;26:351–356.

    Article  CAS  Google Scholar 

  50. 50.

    Kilian M, Heukamp I, Gregor JI, et al. N-3, n-6, and n-9 polyunsaturated fatty acids–which composition in parenteral nutrition decreases severity of acute hemorrhagic necrotizing pancreatitis in rats? Int J Colorectal Dis. 2006;21:57–63.

    PubMed  Article  CAS  Google Scholar 

  51. 51.

    Park KS, Lim JW, Kim H. Inhibitory mechanism of omega-3 fatty acids in pancreatic inflammation and apoptosis. Ann NY Acad Sci. 2009;1171:421–427.

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Weylandt KH, Nadolny A, Kahlke L, et al. Reduction of inflammation and chronic tissue damage by omega-3 fatty acids in fat-1 transgenic mice with pancreatitis. Biochim Biophys Acta. 2008;1782:634–641.

    PubMed  CAS  Google Scholar 

  53. 53.

    Wang X, Li W, Li N, Li J. ω-3 fatty acids-supplemenated parentral nutrition decreases hyperinflammatory response and attenuates systemic disease sequelae in severe acute pancreatitis: A randomized and controlled study. J Parenter Enteral Nutr. 2008;32:236–241.

    Article  CAS  Google Scholar 

  54. 54.

    Pearce CB, Sadek SA, Walters AM, et al. A double-blind, randomized, controlled trail to study the effect of an enteral feed supplemented with glutamine, arginine, and omega-3 fatty acids in predicted acute severe pancreatitis. JOP. 2006;7:361–371.

    PubMed  Google Scholar 

  55. 55.

    Duda MK, O’Shea KM, Tintinu A, et al. Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction. Cardiovasc Res. 2009;81:319–327.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Nicholas J. Zyromski.

Additional information

Supported by the Society for Surgery of the Alimentary Tract Career Development Award (Nicholas J. Zyromski).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Al-Azzawi, H.H., Wade, T.E., Swartz-Basile, D.A. et al. Acute Pancreatitis in Obesity: Adipokines and Dietary Fish Oil. Dig Dis Sci 56, 2318–2325 (2011).

Download citation


  • Adiponectin
  • Pancreatitis
  • Obesity
  • Omega-3 fatty acids