Alteration of adipose tissue immune cell milieu towards the suppression of inflammation in high fat diet fed mice by flaxseed oil supplementation

Autoři: Samina Bashir aff001;  Yadhu Sharma aff001;  Deeba Jairajpuri aff002;  Faraz Rashid aff003;  Md. Nematullah aff001;  Farah Khan aff001
Působiště autorů: Department of Biochemistry, Jamia Hamdard, New Delhi, India aff001;  Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain aff002;  121 DHR, Udyog Vihar, Phase IV, Gurugram, Haryana, India aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223070


The present study evaluates the effect of flaxseed oil (FXO) supplementation on adipose tissue macrophages (ATM’s), E and D series resolvin (Rv) levels and adipose tissue inflammation. Male C57BL/6J mice were divided into five groups (n = 5): lean group (given standard chow diet), HFD group given high fat diet (approx. 18 weeks) till they developed insulin resistance and 4, 8 or 16 mg/kg group (HFD group later orally supplemented with 4, 8 or 16 mg/kg body weight flaxseed oil) for 4 weeks.The present study showed that FXO supplementation led to enhanced DHA, EPA, RvE1-E2, RvD2, RvD5- D6, IL-4, IL-10 and arginase 1 levels in ATMs together with altered immune cell infiltration and reduced NF-κB expression. The FXO supplementation suppresses immune cell infiltration into adipose tissue and alters adipose tissue macrophage phenotype towards the anti-inflammatory state via enhancement of E and D series resolvins, arginase 1 expression and anti-inflammatory cytokines level (IL-4 and IL-10.) leading to amelioration of insulin resistance in flaxseed oil supplemented HFD mice.

Klíčová slova:

Adipose tissue – Cytokines – Fats – Inflammation – Macrophages – Mouse models – Obesity – Oils


1. Shoelson SE, Herrero L, Naaz A (2007) Obesity, inflammation, and insulin resistance. Gastroenterology 132:2169–2180. doi: 10.1053/j.gastro.2007.03.059 17498510

2. Kang YE, Kim JM, Joung KH, Lee JH, You BR, Choi MJ, et al. (2016) The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance in modest obesity and early metabolic dysfunction. PloS one. 11:e0154003. doi: 10.1371/journal.pone.0154003 27101398

3. Parisi L, Gini E, Baci D, Tremolati M, Fanuli M, Bassani B, et al. (2018) Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?. Journal of Immunology Research. 2018.

4. Wen H, Gris D, Lei Y, Jha S(2011) Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signalling. Nat Immunol 12: 408–415. doi: 10.1038/ni.2022 21478880

5. De Boer AA, Monk JM, Liddle DM, Power KA, Ma DW, Robinson LE (2015) Fish Oil-Derived Long-Chain n-3 Polyunsaturated Fatty Acids Reduce Expression of M1-Associated Macrophage Markers in an ex vivo Adipose Tissue Culture Model, in Part through Adiponectin. Front Nutr. 2:31. doi: 10.3389/fnut.2015.00031 26528480

6. Gu Z, Lamont GJ, Lamont RJ, Uriarte SM (2016)Resolvin D1, resolvin D2 and maresin 1 activate the GSK3β anti-inflammatory axis in TLR4-engaged human monocytes. Innate immunity 22: 186–195. doi: 10.1177/1753425916628618 26878867

7. González-Périz A, Horrillo R, Ferré N, Gronert K, Dong B, Morán-Salvador E, et al. (2009) Obesity-induced insulin resistance and hepatic steatosis are alleviated by n-3 fatty acids: a role for resolvins and protectins. The FASEBjournal 23:1946–1957.

8. Spite M, Clària J, Serhan CN(2014)Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. Cell metabolism 19:21–36. doi: 10.1016/j.cmet.2013.10.006 24239568

9. Bashir S, Ali S, Khan F(2015) Partial Reversal of Obesity-Induced Insulin Resistance Owing to Anti-Inflammatory Immunomodulatory Potential of Flaxseed Oil. Immunological Investigations 44: 451–469. doi: 10.3109/08820139.2015.1025960 26107745

10. Pettinelli P, Del Pozo T, Araya J, Rodrigo R, Araya AV, Smok G, et al. (2009) Enhancement in liver SREBP-1c/PPAR-α ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion. Biochimica Et Biophysica Acta (BBA)-molecular basis of disease. 1792:1080–1086.

11. Rincón-Cervera MÁ, Valenzuela R, Hernandez-Rodas MC, Barrera C, Espinosa A, Marambio M, et al. (2016) Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats. Prostaglandins, Leukotrienes and Essential Fatty Acids. 111:25–35.

12. Reagan-Shaw S, Nihal M, Ahmad N(2008) Dose translation from animal to human studies revisited. The FASEB journal 22:659–661. doi: 10.1096/fj.07-9574LSF 17942826

13. Bashir S, Sharma Y, Elahi A, Khan F(2016) Amelioration of obesity-associated inflammation and insulin resistance in c57bl/6 mice via macrophage polarization by fish oil supplementation. The Journal of nutritional biochemistry 33:82–90. doi: 10.1016/j.jnutbio.2016.02.011 27260471

14. Ekström M, Halle M, Bjessmo S, Liska J, Kolak M, Fisher R, et al. (2010) Systemic inflammation activates the nuclear factor-κB regulatory pathway in adipose tissue. American Journal of Physiology-Endocrinology and Metabolism 299: E234–E240. doi: 10.1152/ajpendo.00115.2010 20484010

15. Lee Y.S., Cha B.Y., Choi S.S., Choi B.K., Yonezawa T., Teruya T., et al. (2013) Nobiletin improves obesity and insulin resistance in high-fat diet-induced obese mice.J. Nutr. Biochem. 24:156e162.

16. Sharma Y, Bashir S, Khan MF, Ahmad A, Khan F (2017) Inhibition of Src homology 2 domain containing protein tyrosine phosphatase as the possible mechanism of metformin-assisted amelioration of obesity induced insulin resistance in high fat diet fed C57BL/6J mice. Biochemical and biophysical research communications 487:54–61. doi: 10.1016/j.bbrc.2017.04.012 28389241

17. Livak KJ, Schmittgen TD(2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25:402–408. doi: 10.1006/meth.2001.1262 11846609

18. Colas RA, Shinohara M, Dalli J, Chiang N, Serhan CN (2014) Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. American Journal of Physiology-Cell Physiology 307:C39–54. doi: 10.1152/ajpcell.00024.2014 24696140

19. Pourcet B, Pineda-Torra I(2013) Transcriptional regulation of macrophage arginase 1 expression and its role in atherosclerosis. Trends in cardiovascular medicine 23:143–52. doi: 10.1016/j.tcm.2012.10.003 23375628

20. Kohli P, Levy BD (2009)Resolvins and protectins: mediating solutions to inflammation. British journal of pharmacology 158:960–71. doi: 10.1111/j.1476-5381.2009.00290.x 19594757

21. Castoldi A, Naffah de Souza C, Câmara NO, Moraes-Vieira PM(2016) The macrophage switch in obesity development. Frontiers in immunology 6:637. doi: 10.3389/fimmu.2015.00637 26779183

22. Serhan CN, Hong S, Gronert K, Colgan SP (2002)Resolvins: a family of bioactive products of n-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinammation signals. J Exp Med 196: 1025–1037. doi: 10.1084/jem.20020760 12391014

23. Duvall MG, Levy BD(2016)DHA- and EPA-derived resolvinsprotectins, and maresins in airway inflammation. European Journal of Pharmacology 785:144–155. doi: 10.1016/j.ejphar.2015.11.001 26546247

24. Badawy EA, Rasheed WI, Elias TR, Hussein J, Harvi M, Morsy S, et al. (2015) Flaxseed oil reduces oxidative stress and enhances brain monoamines release in streptozotocin-induced diabetic rats. Hum Exp Toxicol 34:1133–1138. doi: 10.1177/0960327115571765 25669659

25. Nagao K, Yanagita T (2008) Bioactive lipids in metabolic syndrome. Prog Lipid Res. 47:127–146. doi: 10.1016/j.plipres.2007.12.002 18177744

26. Hasturk H, Abdallah R, Kantarci A, Nguyen D, Giordano N, Hamilton J, et al. (2015)Resolvin E1 Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation Induced Atherogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology 35: 1123–1133. doi: 10.1161/ATVBAHA.115.305324 25792445

27. Hasturk H, Kantarci A, Ohira T, Arita M, Ebrahimi N, Chiang N, et al. (2006) RvE1 protects from local inflammation and osteoclast-mediated bone destruction in periodontitis. The FASEB journal 20:401–403. doi: 10.1096/fj.05-4724fje 16373400

28. Arita M, Yoshida M, Hong S, Tjonahen E, Glickman JN, Petasis NA, et al. (2005)Resolvin E1, an endogenous lipid mediator derived from n-3 eicosapentaenoic acid, protects against 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis. Proceedings of the National Academy of Sciences of the United States of America 102:7671–7676. doi: 10.1073/pnas.0409271102 15890784

29. ong S, Lu Y(2013)N-3 fatty acid-derived resolvins and protectins in inflammation resolution and leukocyte functions: targeting novel lipid mediator pathways in mitigation of acute kidney injury. Front Immunol 4:13. doi: 10.3389/fimmu.2013.00013 23386851

30. Qu Q, Xuan W, Fan GH(2015) Roles of resolvins in the resolution of acute inflammation. Cell Biol Int 39:3–22. doi: 10.1002/cbin.10345 25052386

31. Bellenger J, Bellenger S, Bataille A (2011) High Pancreatic n-3 Fatty Acids Prevent STZ-Induced Diabetes in Fat-1 Mice: Inflammatory Pathway Inhibition. Diabetes 60:1090–1099. doi: 10.2337/db10-0901 21330635

32. Fernando MR, Reyes JL, Iannuzzi J, Leung G, McKay DM(2014) The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages. PLoS One 9:e94188. doi: 10.1371/journal.pone.0094188 24736635

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2019 Číslo 10