Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids

Overview

Journal Nutrients

Date 2018 Mar 31

PMID 29601492

Citations 272

Authors

Marcelo Macedo Rogero

Philip C Calder

Affiliations

Soon will be listed here.

Abstract

Obesity leads to an inflammatory condition that is directly involved in the etiology of cardiovascular diseases, type 2 diabetes mellitus, and certain types of cancer. The classic inflammatory response is an acute reaction to infections or to tissue injuries, and it tends to move towards resolution and homeostasis. However, the inflammatory process that was observed in individuals affected by obesity and metabolic syndrome differs from the classical inflammatory response in certain respects. This inflammatory process manifests itself systemically and it is characterized by a chronic low-intensity reaction. The toll-like receptor 4 (TLR4) signaling pathway is acknowledged as one of the main triggers of the obesity-induced inflammatory response. The aim of the present review is to describe the role that is played by the TLR4 signaling pathway in the inflammatory response and its modulation by saturated and omega-3 polyunsaturated fatty acids. Studies indicate that saturated fatty acids can induce inflammation by activating the TLR4 signaling pathway. Conversely, omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, exert anti-inflammatory actions through the attenuation of the activation of the TLR4 signaling pathway by either lipopolysaccharides or saturated fatty acids.

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References

Calder P . The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability. Mol Nutr Food Res. 2012; 56(7):1073-80. DOI: 10.1002/mnfr.201100710. View

Pandey S, Kawai T, Akira S . Microbial sensing by Toll-like receptors and intracellular nucleic acid sensors. Cold Spring Harb Perspect Biol. 2014; 7(1):a016246. PMC: 4292165. DOI: 10.1101/cshperspect.a016246. View

Simopoulos A, DiNicolantonio J . The importance of a balanced ω-6 to ω-3 ratio in the prevention and management of obesity. Open Heart. 2016; 3(2):e000385. PMC: 5093368. DOI: 10.1136/openhrt-2015-000385. View

Holland W, Bikman B, Wang L, Yuguang G, Sargent K, Bulchand S . Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J Clin Invest. 2011; 121(5):1858-70. PMC: 3083776. DOI: 10.1172/JCI43378. View

Dobrovolskaia M, Vogel S . Toll receptors, CD14, and macrophage activation and deactivation by LPS. Microbes Infect. 2002; 4(9):903-14. DOI: 10.1016/s1286-4579(02)01613-1. View

Backhed F, Manchester J, Semenkovich C, Gordon J . Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007; 104(3):979-84. PMC: 1764762. DOI: 10.1073/pnas.0605374104. View

Puglisi M, Hasty A, Saraswathi V . The role of adipose tissue in mediating the beneficial effects of dietary fish oil. J Nutr Biochem. 2010; 22(2):101-8. PMC: 3038466. DOI: 10.1016/j.jnutbio.2010.07.003. View

Hotamisligil G, Shargill N, Spiegelman B . Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993; 259(5091):87-91. DOI: 10.1126/science.7678183. View

Calder P . Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochim Biophys Acta. 2014; 1851(4):469-84. DOI: 10.1016/j.bbalip.2014.08.010. View

10.

Ertunc M, Hotamisligil G . Lipid signaling and lipotoxicity in metaflammation: indications for metabolic disease pathogenesis and treatment. J Lipid Res. 2016; 57(12):2099-2114. PMC: 5321214. DOI: 10.1194/jlr.R066514. View

11.

Endres S, Meydani S, Ghorbani R, Schindler R, Dinarello C . Dietary supplementation with n-3 fatty acids suppresses interleukin-2 production and mononuclear cell proliferation. J Leukoc Biol. 1993; 54(6):599-603. View

12.

Molfino A, Amabile M, Monti M, Muscaritoli M . Omega-3 Polyunsaturated Fatty Acids in Critical Illness: Anti-Inflammatory, Proresolving, or Both?. Oxid Med Cell Longev. 2017; 2017:5987082. PMC: 5488236. DOI: 10.1155/2017/5987082. View

13.

Cinti S . The adipose organ. Prostaglandins Leukot Essent Fatty Acids. 2005; 73(1):9-15. DOI: 10.1016/j.plefa.2005.04.010. View

14.

Calder P . Omega-3 fatty acids and inflammatory processes. Nutrients. 2012; 2(3):355-374. PMC: 3257651. DOI: 10.3390/nu2030355. View

15.

Snodgrass R, Huang S, Choi I, Rutledge J, Hwang D . Inflammasome-mediated secretion of IL-1β in human monocytes through TLR2 activation; modulation by dietary fatty acids. J Immunol. 2013; 191(8):4337-47. PMC: 3825708. DOI: 10.4049/jimmunol.1300298. View

16.

Turnbaugh P, Backhed F, Fulton L, Gordon J . Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008; 3(4):213-23. PMC: 3687783. DOI: 10.1016/j.chom.2008.02.015. View

17.

Backhed F, Ding H, Wang T, Hooper L, Koh G, Nagy A . The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004; 101(44):15718-23. PMC: 524219. DOI: 10.1073/pnas.0407076101. View

18.

Calder P, Yaqoob P . Understanding omega-3 polyunsaturated fatty acids. Postgrad Med. 2009; 121(6):148-57. DOI: 10.3810/pgm.2009.11.2083. View

19.

Hartweg J, Farmer A, Holman R, Neil A . Potential impact of omega-3 treatment on cardiovascular disease in type 2 diabetes. Curr Opin Lipidol. 2009; 20(1):30-8. DOI: 10.1097/mol.0b013e328321b3be. View

20.

van Marken Lichtenbelt W, Vanhommerig J, Smulders N, Drossaerts J, Kemerink G, Bouvy N . Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009; 360(15):1500-8. DOI: 10.1056/NEJMoa0808718. View