Worldwide obesity rates have reached epidemic proportions and significantly contribute to the growing prevalence of metabolic diseases. Chronic low-grade inflammation, a hallmark of obesity, involves immune cell infiltration into expanding adipose tissue. In turn, obesity-associated inflammation can lead to complications in other metabolic tissues (e.g., liver, skeletal muscle, pancreas) through lipotoxicity and inflammatory signaling networks. Importantly, although numerous signaling pathways are known to integrate metabolic and inflammatory processes, the nucleotide-binding and oligomerization domain–like receptor, leucine-rich repeat and pyrin domain–containing 3 (NLRP3) inflammasome is now noted to be a key regulator of metabolic inflammation. The NLRP3 inflammasome can be influenced by various metabolites, including fatty acids. Specifically, although saturated fatty acids may promote NLRP3 inflammasome activation, monounsaturated fatty acids and polyunsaturated fatty acids have recently been shown to impede NLRP3 activity. Therefore, the NLRP3 inflammasome and associated metabolic inflammation have key roles in the relationships among fatty acids, metabolites, and metabolic disease. This review focuses on the ability of fatty acids to influence inflammation and the NLRP3 inflammasome across numerous metabolic tissues in the body. In addition, we explore some perspectives for the future, wherein recent work in the immunology field clearly demonstrates that metabolic reprogramming defines immune cell functionality. Although there is a paucity of information about how diet and fatty acids modulate this process, it is possible that this will open up a new avenue of research relating to nutrient-sensitive metabolic inflammation.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Adams JM, Pratipanawatr T, Berria R, Wang E, DeFronzo RA. 1.  et al. 2004. Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 53:25–31 [Google Scholar]
  2. Ahima RS, Lazar MA. 2.  2013. The health risk of obesity—better metrics imperative. Science 341:856–58 [Google Scholar]
  3. Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H. 3.  et al. 2011. Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. J. Allergy Clin. Immunol. 127:701–21.e70 [Google Scholar]
  4. Arend WP, Guthridge CJ. 4.  2000. Biological role of interleukin 1 receptor antagonist isoforms. Ann. Rheum. Dis. 59:i60–64 [Google Scholar]
  5. Asrih M, Jornayvaz FR. 5.  2013. Inflammation as a potential link between nonalcoholic fatty liver disease and insulin resistance. J. Endocrinol. 218:R25–36 [Google Scholar]
  6. Babio N, Bulló M, Basora J, Martínez-González MA, Fernández-Ballart J. 6.  et al. 2009. Adherence to the Mediterranean diet and risk of metabolic syndrome and its components. Nutr. Metab. Cardiovasc. Dis. 19:563–70 [Google Scholar]
  7. Bauernfeind F, Horvath G, Stutz A, Alnemri ES, MacDonald K. 7.  et al. 2009. NF-κB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol. 183:787–91 [Google Scholar]
  8. Bendtzen K, Mandrup-Poulsen T, Nerup J, Nielsen J, Dinarello C, Svenson M. 8.  1986. Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans. Science 232:1545–47 [Google Scholar]
  9. Benetti E, Chiazza F, Patel NS, Collino M. 9.  2013. The NLRP3 inflammasome as a novel player of the intercellular crosstalk in metabolic disorders. Mediators Inflamm 2013:678627 [Google Scholar]
  10. Blok WL, Deslypere JP, Demacker PNM, van der Ven-Jongekrijg J, Hectors MPC. 10.  et al. 1997. Pro- and anti-inflammatory cytokines in healthy volunteers fed various doses of fish oil for 1 year. Eur. J. Clin. Investig. 27:1003–8 [Google Scholar]
  11. Bradley RL, Fisher FM, Maratos-Flier E. 11.  2008. Dietary fatty acids differentially regulate production of TNF-α and IL-10 by murine 3T3-L1 adipocytes. Obesity 16:938–44 [Google Scholar]
  12. Brehm BJ, Lattin BL, Summer SS, Boback JA, Gilchrist GM. 12.  et al. 2009. One-year comparison of a high–monounsaturated fat diet with a high-carbohydrate diet in type 2 diabetes. Diabetes Care 32:215–20 [Google Scholar]
  13. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L. 13.  et al. 2005. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat. Med. 11:183–90 [Google Scholar]
  14. Camell CD, Nguyen KY, Jurczak MJ, Christian BE, Shulman GI. 14.  et al. 2015. Macrophage-specific de novo synthesis of ceramide is dispensable for inflammasome-driven inflammation and insulin resistance in obesity. J. Biol. Chem. 290:29402–13 [Google Scholar]
  15. Canfora EE, Jocken JW, Blaak EE. 15.  2015. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat. Rev. Endocrinol. 11:577–91 [Google Scholar]
  16. Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG. 16.  et al. 2006. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55:2688–97 [Google Scholar]
  17. Chan KL, Pillon NJ, Sivaloganathan DM, Costford SR, Liu Z. 17.  et al. 2015. Palmitoleate reverses high fat-induced proinflammatory macrophage polarization via AMP-activated protein kinase (AMPK). J. Biol. Chem. 290:16979–88 [Google Scholar]
  18. Chan MM-Y. 18.  1995. Inhibition of tumor necrosis factor by curcumin, a phytochemical. Biochem. Pharmacol. 49:1551–56 [Google Scholar]
  19. Cho KA, Kang PB. 19.  2015. PLIN2 inhibits insulin-induced glucose uptake in myoblasts through the activation of the NLRP3 inflammasome. Int. J. Mol. Med. 36:839–44 [Google Scholar]
  20. Choi YK, Kim MK, Bae KH, Seo HA, Jeong JY. 20.  et al. 2013. Serum irisin levels in new-onset type 2 diabetes. Diabetes Res. Clin. Pract. 100:96–101 [Google Scholar]
  21. Chrysohoou C, Panagiotakos DB, Pitsavos C, Das UN, Stefanadis C. 21.  2004. Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the Attica study. J. Am. Coll. Cardiol. 44:152–58 [Google Scholar]
  22. Coll RC, Robertson AAB, Chae JJ, Higgins SC, Munoz-Planillo R. 22.  et al. 2015. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 21:248–55 [Google Scholar]
  23. Dai J, Miller AH, Bremner JD, Goldberg J, Jones L. 23.  et al. 2008. Adherence to the Mediterranean Diet is inversely associated with circulating interleukin-6 among middle-aged men: a twin study. Circulation 117:169–75 [Google Scholar]
  24. De Boer AA, Monk JM, Liddle DM, Hutchinson AL, Power KA. 24.  et al. 2016. Fish-oil-derived n-3 polyunsaturated fatty acids reduce NLRP3 inflammasome activity and obesity-related inflammatory cross-talk between adipocytes and CD11b+ macrophages. J. Nutr. Biochem. 34:61–72 [Google Scholar]
  25. DeFronzo RA, Tripathy D. 25.  2009. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 32:Suppl. 2S157–63 [Google Scholar]
  26. Delerive P, Bosscher KD, Berghe WV, Fruchart J-C, Haegeman G, Staels B. 26.  2002. DNA binding–independent induction of IκBα gene transcription by PPARα. ;. Mol. Endocrinol. 16:1029–39 [Google Scholar]
  27. Dinarello CA. 27.  2009. Immunological and inflammatory functions of the interleukin-1 family. Annu. Rev. Immunol. 27:519–50 [Google Scholar]
  28. Dixon LJ, Flask CA, Papouchado BG, Feldstein AE, Nagy LE. 28.  2013. Caspase-1 as a central regulator of high fat diet–induced non-alcoholic steatohepatitis. PLOS ONE 8:e56100 [Google Scholar]
  29. Dong J, Dong Y, Dong Y, Chen F, Mitch WE, Zhang L. 29.  2016. Inhibition of myostatin in mice improves insulin sensitivity via irisin-mediated cross talk between muscle and adipose tissues. Int. J. Obes. 40:434–42 [Google Scholar]
  30. Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S. 30.  et al. 1999. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J. Clin. Investig. 103:253–59 [Google Scholar]
  31. Dunne A, Ross PJ, Pospisilova E, Masin J, Meaney A. 31.  et al. 2010. Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis. . J. Immunol. 185:1711–19 [Google Scholar]
  32. El-Assaad W, Buteau J, Peyot M-L, Nolan C, Roduit R. 32.  et al. 2003. Saturated fatty acids synergize with elevated glucose to cause pancreatic β-cell death. Endocrinology 144:4154–63 [Google Scholar]
  33. Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G. 33.  et al. 1989. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N. Engl. J. Med. 320:265–71 [Google Scholar]
  34. Ertunc ME, Hotamisligil GS. 34.  2016. Lipid signaling and lipotoxicity in metabolic inflammation: indications for metabolic disease pathogenesis and treatment. J. Lipid Res. 57:2099–114 [Google Scholar]
  35. Esposito K, Pontillo A, Ciotola M, Palo CD, Grella E. 35.  et al. 2002. Weight loss reduces interleukin-18 levels in obese women. J. Clin. Endocrinol. Metab. 87:3864–66 [Google Scholar]
  36. Fain JN, Bahouth SW, Madan AK. 36.  2005. Involvement of multiple signaling pathways in the post-bariatric induction of IL-6 and IL-8 mRNA and release in human visceral adipose tissue. Biochem. Pharmacol. 69:1315–24 [Google Scholar]
  37. Farrell GC, Larter CZ. 37.  2006. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43:Suppl. 1S99–112 [Google Scholar]
  38. Febbraio MA. 38.  2014. Role of interleukins in obesity: implications for metabolic disease. Trends Endocrinol. Metab. 25:312–19 [Google Scholar]
  39. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J. 39.  et al. 2009. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med. 15:930–39 [Google Scholar]
  40. Fex M, Nitert MD, Wierup N, Sundler F, Ling C, Mulder H. 40.  2007. Enhanced mitochondrial metabolism may account for the adaptation to insulin resistance in islets from C57BL/6J mice fed a high-fat diet. Diabetologia 50:74–83 [Google Scholar]
  41. Filardy AA, He J, Bennink J, Yewdell J, Kelsall BL. 41.  2016. Posttranscriptional control of NLRP3 inflammasome activation in colonic macrophages. Mucosal Immunol 9:850–58 [Google Scholar]
  42. Finucane OM, Lyons CL, Murphy AM, Reynolds CM, Klinger R. 42.  et al. 2015. Monounsaturated fatty acid–enriched high-fat diets impede adipose NLRP3 inflammasome–mediated IL-1β secretion and insulin resistance despite obesity. Diabetes 64:2116–28 [Google Scholar]
  43. Flower L, Gray R, Pinkney J, Mohamed-Ali V. 43.  2003. Stimulation of interleukin-6 release by interleukin-1β from isolated human adipocytes. Cytokine 21:32–37 [Google Scholar]
  44. Fowler BJ, Gelfand BD, Kim Y, Kerur N, Tarallo V. 44.  et al. 2014. Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity. Science 346:1000–3 [Google Scholar]
  45. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y. 45.  et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Investig. 114:1752–61 [Google Scholar]
  46. Garcia MC, Wernstedt I, Berndtsson A, Enge M, Bell M. 46.  et al. 2006. Mature-onset obesity in interleukin-1 receptor I knockout mice. Diabetes 55:1205–13 [Google Scholar]
  47. Glass CK, Olefsky JM. 47.  2012. Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab 15:635–45 [Google Scholar]
  48. Goldin A, Beckman JA, Schmidt AM, Creager MA. 48.  2006. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114:597–605 [Google Scholar]
  49. Gregor MF, Hotamisligil GS. 49.  2011. Inflammatory mechanisms in obesity. Annu. Rev. Immunol. 29:415–45 [Google Scholar]
  50. Grimm H, Mayer K, Mayser P, Eigenbrodt E. 50.  2002. Regulatory potential of n-3 fatty acids in immunological and inflammatory processes. Br. J. Nutr. 87:Suppl. 1S59–67 [Google Scholar]
  51. Guo H, Callaway JB, Ting JPY. 51.  2015. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat. Med. 21:677–87 [Google Scholar]
  52. Guo W, Wong S, Xie W, Lei T, Luo Z. 52.  2007. Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes. Am. J. Physiol. Endocrinol. Metab. 293:E576–86 [Google Scholar]
  53. Hardy T, Oakley F, Anstee QM, Day CP. 53.  2016. Nonalcoholic fatty liver disease: pathogenesis and disease spectrum. Annu. Rev. Pathol. 11:451–96 [Google Scholar]
  54. Healy NP, Kirwan AM, McArdle MA, Holohan K, Nongonierma AB. 54.  et al. 2016. A casein hydrolysate protects mice against high fat diet induced hyperglycemia by attenuating NLRP3 inflammasome–mediated inflammation and improving insulin signaling. Mol. Nutr. Food Res. 60:2421–32 [Google Scholar]
  55. Hirota SA, Ng J, Lueng A, Khajah M, Parhar K. 55.  et al. 2011. NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. Inflamm. Bowel Dis. 17:1359–72 [Google Scholar]
  56. Holland WL, Bikman BT, Wang L-P, Yuguang G, Sargent KM. 56.  et al. 2011. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid–induced ceramide biosynthesis in mice. J. Clin. Investig. 121:1858–70 [Google Scholar]
  57. Honda H, Nagai Y, Takatsu K. 57.  2013. Isoliquiritigenin and glycyrrhizin inhibit the inflammasome activation in a different manner. J. Immunol. 190:Suppl.116.1 [Google Scholar]
  58. Hotamisligil GS. 58.  2006. Inflammation and metabolic disorders. Nature 444:860–67 [Google Scholar]
  59. Hussey SE, Lum H, Alvarez A, Cipriani Y, Garduño-Garcia J. 59.  et al. 2014. A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle. Diabetologia 57:582–91 [Google Scholar]
  60. Iacobazzi V, Infantino V. 60.  2014. Citrate—new functions for an old metabolite. Biol. Chem. 395:387–99 [Google Scholar]
  61. Ignacio A, Morales CI, Câmara NOS, Almeida RR. 61.  2016. Innate sensing of the gut microbiota: modulation of inflammatory and autoimmune diseases. Front. Immunol. 7:54 [Google Scholar]
  62. Isoda K, Sawada S, Ayaori M, Matsuki T, Horai R. 62.  et al. 2005. Deficiency of interleukin-1 receptor antagonist deteriorates fatty liver and cholesterol metabolism in hypercholesterolemic mice. J. Biol. Chem. 280:7002–9 [Google Scholar]
  63. Itani SI, Ruderman NB, Schmieder F, Boden G. 63.  2002. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α. ;. Diabetes 51:2005–11 [Google Scholar]
  64. Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R. 64.  et al. 2003. Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40. Nature 422:173–76 [Google Scholar]
  65. Jellema A, Plat J, Mensink RP. 65.  2004. Weight reduction, but not a moderate intake of fish oil, lowers concentrations of inflammatory markers and PAI-1 antigen in obese men during the fasting and postprandial state. Eur. J. Clin. Investig. 34:766–73 [Google Scholar]
  66. Jha AK, Huang SC-C, Sergushichev A, Lampropoulou V, Ivanova Y. 66.  et al. 2015. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42:419–30 [Google Scholar]
  67. Karastergiou K, Mohamed-Ali V. 67.  2010. The autocrine and paracrine roles of adipokines. Mol. Cell. Endocrinol. 318:69–78 [Google Scholar]
  68. Kien CL, Bunn JY, Tompkins CL, Dumas JA, Crain KI. 68.  et al. 2013. Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood. Am. J. Clin. Nutr. 97:689–97 [Google Scholar]
  69. Kopelman PG. 69.  2000. Obesity as a medical problem. Nature 404:635–43 [Google Scholar]
  70. Kotas ME, Jurczak MJ, Annicelli C, Gillum MP, Cline GW. 70.  et al. 2013. Role of caspase-1 in regulation of triglyceride metabolism. PNAS 110:4810–15 [Google Scholar]
  71. Kraakman MJ, Kammoun HL, Allen TL, Deswaerte V, Henstridge DC. 71.  et al. 2015. Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance. Cell Metab 21:403–16 [Google Scholar]
  72. Krahmer N, Farese RV, Walther TC. 72.  2013. Balancing the fat: lipid droplets and human disease. EMBO Mol. Med. 5:905–15 [Google Scholar]
  73. Lagathu C, Yvan-Charvet L, Bastard JP, Maachi M, Quignard-Boulangé A. 73.  et al. 2006. Long-term treatment with interleukin-1β induces insulin resistance in murine and human adipocytes. Diabetologia 49:2162–73 [Google Scholar]
  74. Lamkanfi M, Dixit VM. 74.  2012. Inflammasomes and their roles in health and disease. Annu. Rev. Cell Dev. Biol. 28:137–61 [Google Scholar]
  75. Lamkanfi M, Dixit VM. 75.  2014. Mechanisms and functions of inflammasomes. Cell 157:1013–22 [Google Scholar]
  76. Larsen CM, Faulenbach M, Vaag A, Vølund A, Ehses JA. 76.  et al. 2007. Interleukin-1–receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 356:1517–26 [Google Scholar]
  77. Lee H-M, Kim J-J, Kim HJ, Shong M, Ku BJ, Jo E-K. 77.  2013. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes 62:194–204 [Google Scholar]
  78. Levy M, Thaiss CA, Katz MN, Suez J, Elinav E. 78.  2015. Inflammasomes and the microbiota—partners in the preservation of mucosal homeostasis. Semin. Immunopathol. 37:39–46 [Google Scholar]
  79. Lindegaard B, Matthews VB, Brandt C, Hojman P, Allen TL. 79.  et al. 2013. Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice. Diabetes 62:3064–74 [Google Scholar]
  80. Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P. 80.  2015. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Dig. Liver Dis. 47:181–90 [Google Scholar]
  81. Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR. 81.  2008. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239–46 [Google Scholar]
  82. Lumeng CN, Saltiel AR. 82.  2011. Inflammatory links between obesity and metabolic disease. J. Clin. Investig. 121:2111–17 [Google Scholar]
  83. Lyons CL, Kennedy EB, Roche HM. 83.  2016. Metabolic inflammation—differential modulation by dietary constituents. Nutrients 8:247 [Google Scholar]
  84. Maedler K, Oberholzer J, Bucher P, Spinas GA, Donath MY. 84.  2003. Monounsaturated fatty acids prevent the deleterious effects of palmitate and high glucose on human pancreatic β-cell turnover and function. Diabetes 52:726–33 [Google Scholar]
  85. Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI. 85.  et al. 2002. Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets. J. Clin. Investig. 110:851–60 [Google Scholar]
  86. Masters SL, Dunne A, Subramanian SL, Hull RL, Tannahill GM. 86.  et al. 2010. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nat. Immunol. 11:897–904 [Google Scholar]
  87. Matsuki T, Horai R, Sudo K, Iwakura Y. 87.  2003. IL-1 plays an important role in lipid metabolism by regulating insulin levels under physiological conditions. J. Exp. Med. 198:877–88 [Google Scholar]
  88. McArdle MA, Finucane OM, Connaughton RM, McMorrow AM, Roche HM. 88.  2013. Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies. Front. Endocrinol. 4:52 [Google Scholar]
  89. McGillicuddy FC, Harford KA, Reynolds CM, Oliver E, Claessens M. 89.  et al. 2011. Lack of interleukin-1 receptor I (IL-1RI) protects mice from high-fat diet–induced adipose tissue inflammation coincident with improved glucose homeostasis. Diabetes 60:1688–98 [Google Scholar]
  90. McGillicuddy FC, Reynolds CM, Finucane O, Coleman E, Harford KA. 90.  et al. 2013. Long-term exposure to a high-fat diet results in the development of glucose intolerance and insulin resistance in interleukin-1 receptor I–deficient mice. Am. J. Physiol. Endocrinol. Metab. 305:E834–44 [Google Scholar]
  91. Meier CA, Bobbioni E, Gabay C, Assimacopoulos-Jeannet F, Golay A, Dayer J-M. 91.  2002. IL-1 receptor antagonist serum levels are increased in human obesity: a possible link to the resistance to leptin?. J. Clin. Endocrinol. Metab. 87:1184–88 [Google Scholar]
  92. Mills KHG, Dunne A. 92.  2009. Immune modulation: IL-1, master mediator or initiator of inflammation. Nat. Med. 15:1363–64 [Google Scholar]
  93. Moon J-S, Nakahira K, Choi AMK. 93.  2015. Fatty acid synthesis and NLRP3-inflammasome. Oncotarget 6:21765–66 [Google Scholar]
  94. Mori TA, Woodman RJ, Burke V, Puddey IB, Croft KD, Beilin LJ. 94.  2003. Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated–hypertensive type 2 diabetic subjects. Free Radic. Biol. Med. 35:772–81 [Google Scholar]
  95. Morrison MC, Mulder P, Salic K, Verheij J, Liang W. 95.  et al. 2016. Intervention with a caspase-1 inhibitor reduces obesity-associated hyperinsulinemia, non-alcoholic steatohepatitis and hepatic fibrosis in LDLR−/−.Leiden mice. Int. J. Obes. 40:1416–23 [Google Scholar]
  96. Murphy AJ, Kraakman MJ, Kammoun HL, Dragoljevic D, Lee MKS. 96.  et al. 2016. IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome. Cell Metab 23:155–64 [Google Scholar]
  97. Murphy AM, Lyons CL, Finucane OM, Roche HM. 97.  2015. Interactions between differential fatty acids and inflammatory stressors—impact on metabolic health. Prostaglandins Leukot. Essent. Fat. Acids 92:49–55 [Google Scholar]
  98. Netea MG, Joosten LA, Lewis E, Jensen DR, Voshol PJ. 98.  et al. 2006. Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nat. Med. 12:650–56 [Google Scholar]
  99. Netea MG, Nold-Petry CA, Nold MF, Joosten LA, Opitz B. 99.  et al. 2009. Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages. Blood 113:2324–35 [Google Scholar]
  100. Neuhofer A, Zeyda M, Mascher D, Itariu BK, Murano I. 100.  et al. 2013. Impaired local production of proresolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation. Diabetes 62:1945–56 [Google Scholar]
  101. Oliver E, McGillicuddy FC, Harford KA, Reynolds CM, Phillips CM. 101.  et al. 2012. Docosahexaenoic acid attenuates macrophage-induced inflammation and improves insulin sensitivity in adipocytes—specific differential effects between LC n-3 PUFA. J. Nutr. Biochem. 23:1192–200 [Google Scholar]
  102. Ong JDH, Mansell A, Tate MD. 102.  2017. Hero turned villain: NLRP3 inflammasome–induced inflammation during influenza A virus infection. J. Leukoc. Biol. In press. https://doi.org/10.1189/jlb.4MR0616-288R [Crossref]
  103. Oster RT, Tishinsky JM, Yuan Z, Robinson LE. 103.  2010. Docosahexaenoic acid increases cellular adiponectin mRNA and secreted adiponectin protein, as well as PPARγ mRNA, in 3T3-L1 adipocytes. Appl. Physiol. Nutr. Metab. 35:783–89 [Google Scholar]
  104. Palsson-McDermott EM, Curtis AM, Goel G, Lauterbach MAR, Sheedy FJ. 104.  et al. 2015. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages. Cell Metab 21:65–80 [Google Scholar]
  105. Patterson E, O'Doherty RM, Murphy EF, Wall R, O'Sullivan O. 105.  et al. 2014. Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in C57BL/6J mice. Br. J. Nutr. 111:1905–17 [Google Scholar]
  106. Pedersen BK, Febbraio MA. 106.  2008. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol. Rev. 88:1379–406 [Google Scholar]
  107. Perreault M, Roke K, Badawi A, Nielsen DE, Abdelmagid SA. 107.  et al. 2014. Plasma levels of 14:0, 16:0, 16:1n-7, and 20:3n-6 are positively associated, but 18:0 and 18:2n-6 are inversely associated with markers of inflammation in young healthy adults. Lipids 49:255–63 [Google Scholar]
  108. Pilon G, Dallaire P, Marette A. 108.  2004. Inhibition of inducible nitric-oxide synthase by activators of AMP-activated protein kinase: a new mechanism of action of insulin-sensitizing drugs. J. Biol. Chem. 279:20767–74 [Google Scholar]
  109. Poitout V, Amyot J, Semache M, Zarrouki B, Hagman D, Fontés G. 109.  2010. Glucolipotoxicity of the pancreatic β cell. Biochim. Biophys. Acta 1801:289–98 [Google Scholar]
  110. Raichur S, Wang ST, Chan PW, Li Y, Ching J. 110.  et al. 2014. CerS2 haploinsufficiency inhibits β-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance. Cell Metab 20:687–95 [Google Scholar]
  111. Ralston JC, Matravadia S, Gaudio N, Holloway GP, Mutch DM. 111.  2015. Polyunsaturated fatty acid regulation of adipocyte FADS1 and FADS2 expression and function. Obesity 23:725–28 [Google Scholar]
  112. Ralston JC, Metherel AH, Stark KD, Mutch DM. 112.  2016. SCD1 mediates the influence of exogenous saturated and monounsaturated fatty acids in adipocytes: effects on cellular stress, inflammatory markers and fatty acid elongation. J. Nutr. Biochem. 27:241–48 [Google Scholar]
  113. Reynolds CM, McGillicuddy FC, Harford KA, Finucane OM, Mills KH, Roche HM. 113.  2012. Dietary saturated fatty acids prime the NLRP3 inflammasome via TLR4 in dendritic cells—implications for diet-induced insulin resistance. Mol. Nutr. Food Res. 56:1212–22 [Google Scholar]
  114. Robertson RP, Harmon J, Tran PO, Poitout V. 114.  2004. β-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 53:Suppl. 1S119–24 [Google Scholar]
  115. Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. 115.  2003. Glucose toxicity in β-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 52:581–87 [Google Scholar]
  116. Roke K, Ralston JC, Abdelmagid S, Nielsen DE, Badawi A. 116.  et al. 2013. Variation in the FADS1/2 gene cluster alters plasma n−6 PUFA and is weakly associated with hsCRP levels in healthy young adults. Prostaglandins Leukot. Essent. Fat. Acids 89:257–63 [Google Scholar]
  117. Round JL, Mazmanian SK. 117.  2009. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9:313–23 [Google Scholar]
  118. Rui L. 118.  2014. Energy metabolism in the liver. Compr. Physiol. 4:177–97 [Google Scholar]
  119. Sadagopan N, Li W, Roberds SL, Major T, Preston GM. 119.  et al. 2007. Circulating succinate is elevated in rodent models of hypertension and metabolic disease. Am. J. Hypertens. 20:1209–15 [Google Scholar]
  120. Sauter NS, Schulthess FT, Galasso R, Castellani LW, Maedler K. 120.  2008. The antiinflammatory cytokine interleukin-1 receptor antagonist protects from high-fat diet-induced hyperglycemia. Endocrinology 149:2208–18 [Google Scholar]
  121. Savage DB, Petersen KF, Shulman GI. 121.  2007. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol. Rev. 87:507–20 [Google Scholar]
  122. Schilling JD, Machkovech HM, He L, Sidhu R, Fujiwara H. 122.  et al. 2013. Palmitate and lipopolysaccharide trigger synergistic ceramide production in primary macrophages. J. Biol. Chem. 288:2923–32 [Google Scholar]
  123. Schroder K, Zhou R, Tschopp J. 123.  2010. The NLRP3 inflammasome: a sensor for metabolic danger?. Science 327:296–300 [Google Scholar]
  124. Seo S-U, Kamada N, Muñoz-Planillo R, Kim Y-G, Kim D. 124.  et al. 2015. Distinct commensals induce interleukin-1β via NLRP3 inflammasome in inflammatory monocytes to promote intestinal inflammation in response to injury. Immunity 42:744–55 [Google Scholar]
  125. Shaw B, Lambert S, Wong MH, Ralston JC, Stryjecki C, Mutch DM. 125.  2013. Individual saturated and monounsaturated fatty acids trigger distinct transcriptional networks in differentiated 3T3-L1 preadipocytes. J. Nutrigenet. Nutrigenomics 6:1–15 [Google Scholar]
  126. Shiratsuchi A, Ichiki M, Okamoto Y, Ueda N, Sugimoto N. 126.  et al. 2009. Inhibitory effect of N-palmitoylphosphatidylethanolamine on macrophage phagocytosis through inhibition of Rac1 and Cdc42. J. Biochem. 145:43–50 [Google Scholar]
  127. Singh S, Aggarwal BB. 127.  1995. Activation of transcription factor NF-κB is suppressed by curcumin (diferuloylmethane). J. Biol. Chem. 270:24995–5000 [Google Scholar]
  128. Siriwardhana N, Kalupahana NS, Fletcher S, Xin W, Claycombe KJ. 128.  et al. 2012. n-3 and n-6 polyunsaturated fatty acids differentially regulate adipose angiotensinogen and other inflammatory adipokines in part via NF-κB-dependent mechanisms. J. Nutr. Biochem. 23:1661–67 [Google Scholar]
  129. Song-Zhao GX, Srinivasan N, Pott J, Baban D, Frankel G, Maloy KJ. 129.  2014. Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen. Mucosal Immunol 7:763–74 [Google Scholar]
  130. Stienstra R, Joosten LAB, Koenen T, van Tits B, van Diepen JA. 130.  et al. 2010. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab 12:593–605 [Google Scholar]
  131. Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL. 131.  et al. 2011. Inflammasome is a central player in the induction of obesity and insulin resistance. PNAS 108:15324–29 [Google Scholar]
  132. Stryjecki C, Roke K, Clarke S, Nielsen D, Badawi A. 132.  et al. 2012. Enzymatic activity and genetic variation in SCD1 modulate the relationship between fatty acids and inflammation. Mol. Genet. Metab. 105:421–27 [Google Scholar]
  133. Stylianou E, Saklatvala J. 133.  1998. Interleukin-1. Int. J. Biochem. Cell Biol. 30:1075–79 [Google Scholar]
  134. Sun Z, Lazar MA. 134.  2013. Dissociating fatty liver and diabetes. Trends Endocrinol. Metab. 24:4–12 [Google Scholar]
  135. Tack CJ, Stienstra R, Joosten LAB, Netea MG. 135.  2012. Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family. Immunol. Rev. 249:239–52 [Google Scholar]
  136. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF. 136.  et al. 2013. Succinate is a danger signal that induces IL-1β via HIF-1α. ;. Nature 496:238–42 [Google Scholar]
  137. Teixeira TFS, Collado MC, Ferreira CLLF, Bressan J, MdoCG Peluzio. 137.  2012. Potential mechanisms for the emerging link between obesity and increased intestinal permeability. Nutr. Res. 32:637–47 [Google Scholar]
  138. Tilg H, Moschen AR. 138.  2008. Inflammatory mechanisms in the regulation of insulin resistance. Mol. Med. 14:222–31 [Google Scholar]
  139. Tilg H, Moschen AR, Szabo G. 139.  2016. Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology 64:955–65 [Google Scholar]
  140. Tsutsui H, Imamura M, Fujimoto J, Nakanishi K. 140.  2010. The TLR4/TRIF-mediated activation of NLRP3 inflammasome underlies endotoxin-induced liver injury in mice. Gastroenterol. Res. Pract. 2010:641865 [Google Scholar]
  141. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. 141.  2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–131 [Google Scholar]
  142. Van Beek M, Oravecz-Wilson KI, Delekta PC, Gu S, Li X. 142.  et al. 2012. Bcl10 links saturated fat overnutrition with hepatocellular NF-κB activation and insulin resistance. Cell Rep 1:444–52 [Google Scholar]
  143. van Diepen JA, Stienstra R, Vroegrijk IO, van den Berg SA, Salvatori D. 143.  et al. 2013. Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion. J. Lipid Res. 54:448–56 [Google Scholar]
  144. van Dijk SJ, Feskens EJ, Bos MB, Hoelen DW, Heijligenberg R. 144.  et al. 2009. A saturated fatty acid–rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome. Am. J. Clin. Nutr. 90:1656–64 [Google Scholar]
  145. van Herpen NA, Schrauwen-Hinderling VB. 145.  2008. Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol. Behav. 94:231–41 [Google Scholar]
  146. Vandanmagsar B, Youm Y-H, Ravussin A, Galgani JE, Stadler K. 146.  et al. 2011. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17:179–88 [Google Scholar]
  147. Vanni E, Bugianesi E, Kotronen A, De Minicis S, Yki-Järvinen H, Svegliati-Baroni G. 147.  2010. From the metabolic syndrome to NAFLD or vice versa?. Dig. Liver Dis. 42:320–30 [Google Scholar]
  148. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL. 148.  et al. 2006. Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation. Cell Metab 4:13–24 [Google Scholar]
  149. Vessby B, Uusitupa M, Hermansen K, Riccardi G, Rivellese AA. 149.  et al. 2001. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU Study. Diabetologia 44:312–19 [Google Scholar]
  150. Vitale A, Cantarini L, Rigante D, Bardelli M, Galeazzi M. 150.  2015. Anakinra treatment in patients with gout and type 2 diabetes. Clin. Rheumatol. 34:981–84 [Google Scholar]
  151. Wang B, Wood IS, Trayhurn P. 151.  2008. Hypoxia induces leptin gene expression and secretion in human preadipocytes: differential effects of hypoxia on adipokine expression by preadipocytes. J. Endocrinol. 198:127–34 [Google Scholar]
  152. Wei Y, Chen K, Whaley-Connell AT, Stump CS, Ibdah JA, Sowers JR. 152.  2008. Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294:R673–80 [Google Scholar]
  153. Weldon SM, Mullen AC, Loscher CE, Hurley LA, Roche HM. 153.  2007. Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. J. Nutr. Biochem. 18:250–58 [Google Scholar]
  154. Wen H, Gris D, Lei Y, Jha S, Zhang L. 154.  et al. 2011. Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat. Immunol. 12:408–15 [Google Scholar]
  155. 155. WHO (World Health Organ.). 2016. Obesity and overweight: fact sheet. Geneva: WHO http://www.who.int/mediacentre/factsheets/fs311/en/
  156. Winer S, Chan Y, Paltser G, Truong D, Tsui H. 156.  et al. 2009. Normalization of obesity-associated insulin resistance through immunotherapy. Nat. Med. 15:921–29 [Google Scholar]
  157. Wolsk E, Mygind H, Grøndahl TS, Pedersen BK, van Hall G. 157.  2010. IL-6 selectively stimulates fat metabolism in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 299:E832–40 [Google Scholar]
  158. Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD. 158.  et al. 2014. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology 59:898–910 [Google Scholar]
  159. Wree A, McGeough MD, Peña CA, Schlattjan M, Li H. 159.  et al. 2014. NLRP3 inflammasome activation is required for fibrosis development in NAFLD. J. Mol. Med. 92:1069–82 [Google Scholar]
  160. Wu Y, Song P, Xu J, Zhang M, Zou M-H. 160.  2007. Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. J. Biol. Chem. 282:9777–88 [Google Scholar]
  161. Yang G, Lee HE, Lee JY. 161.  2016. A pharmacological inhibitor of NLRP3 inflammasome prevents non-alcoholic fatty liver disease in a mouse model induced by high fat diet. Sci. Rep. 6:24399 [Google Scholar]
  162. Yang L, Calay ES, Fan J, Arduini A, Kunz RC. 162.  et al. 2015. S-Nitrosylation links obesity-associated inflammation to endoplasmic reticulum dysfunction. Science 349:500–6 [Google Scholar]
  163. Yao D, Brownlee M. 163.  2010. Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands. Diabetes 59:249–55 [Google Scholar]
  164. Yore MM, Syed I, Moraes-Vieira PM, Zhang T, Herman MA. 164.  et al. 2014. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159:318–32 [Google Scholar]
  165. Youm Y-H, Adijiang A, Vandanmagsar B, Burk D, Ravussin A, Dixit VD. 165.  2011. Elimination of the NLRP3-ASC inflammasome protects against chronic obesity-induced pancreatic damage. Endocrinology 152:4039–45 [Google Scholar]
  166. Youm Y-H, Nguyen KY, Grant RW, Goldberg EL, Bodogai M. 166.  et al. 2015. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat. Med. 21:263–69 [Google Scholar]
  167. Yu C, Chen Y, Cline GW, Zhang D, Zong H. 167.  et al. 2002. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J. Biol. Chem. 277:50230–36 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error