Residential macrophages in adipose tissue play a pivotal role in the development of inflammation not only within this tissue, but also affect the proinflammatory status of the whole body. Data on human adipose tissue inflammation and the role of macrophages are rather scarce. We previously documented that the proportion of proinflammatory macrophages in human adipose tissue correlates closely with non-HDL cholesterol concentrations. We hypothesized that this is due to the identical influence of diet on both parameters and decided to analyze the fatty acid spectrum in cell membrane phospholipids of the same individuals as a parameter of the diet consumed. Proinflammatory and anti-inflammatory macrophages were isolated from human adipose tissue (n = 43) and determined by flow cytometry as CD14+CD16+CD36high and CD14+CD16-CD163+, respectively. The spectrum of fatty acids in phospholipids in the cell membranes of specimens of the same adipose tissue was analyzed, and the proportion of proinflammatory macrophage increased with the proportions of palmitic and palmitoleic acids. Contrariwise, these macrophages decreased with increasing alpha-linolenic acid, total n-3 fatty acids, n-3/n-6 ratio, and eicosatetraenoic acid. A mirror picture was documented for the proportion of anti-inflammatory macrophages. The dietary score, obtained using a food frequency questionnaire, documented a positive relation to proinflammatory macrophages in individuals who consumed predominantly vegetable fat and fish, and individuals who consumed diets based on animal fat without fish and nut consumption. he present data support our hypothesis that macrophage polarization in human visceral adipose tissue is related to fatty acid metabolism, cell membrane composition, and diet consumed. It is suggested that fatty acid metabolism might participate also in inflammation and the risk of developing cardiovascular disease.

Anaestesiology Resuscitation and Intensive Care Unit Military University Hospital 140 21 Prague Czech Republic

Centre for Experimental Medicine Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Transplant Surgery Dept Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

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Int J Obes (Lond). 2021 Oct;45(10):2286-2287. doi: 10.1038/s41366-021-00882-7. PubMed

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Cifkova R., Skodova Z., Bruthans J., Adamkova V., Jozifova M., Galovcova M., Wohlfahrt P., Krajcoviechova A., Poledne R., Stavek P., et al. Longitudinal trends in major cardiovascular risk factors in the Czech population between 1985 and 2007/8. Czech MONICA and Czech post-MONICA. Atherosclerosis. 2010;211:676–681. doi: 10.1016/j.atherosclerosis.2010.04.007. PubMed DOI

Williams E.P., Mesidor M., Winters K., Dubbert P.M., Wyatt S.B. Overweight and Obesity: Prevalence, Consequences, and Causes of a Growing Public Health Problem. Curr. Obes. Rep. 2015;4:363–370. doi: 10.1007/s13679-015-0169-4. PubMed DOI

Kuda O., Rossmeisl M., Kopecky J. Omega-3 fatty acids and adipose tissue biology. Mol. Asp. Med. 2018;64:147–160. doi: 10.1016/j.mam.2018.01.004. PubMed DOI

Mulder R., Banete A., Basta S. Spleen-derived macrophages are readily polarized into classically activated (M1) or alternatively activated (M2) states. Immunobiology. 2014;219:737–745. doi: 10.1016/j.imbio.2014.05.005. PubMed DOI

Weisberg S.P., McCann D., Desai M., Rosenbaum M., Leibel R.L., Ferrante A.W. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Investig. 2003;112:1796–1808. doi: 10.1172/JCI200319246. PubMed DOI PMC

Glass C.K., Witztum J.L. Atherosclerosis: The road ahead. Cell. 2001;104:503–516. doi: 10.1016/S0092-8674(01)00238-0. PubMed DOI

Ramkhelawon B., Hennessy E.J., Menager M., Ray T.D., Sheedy F.J., Hutchison S., Wanschel A., Oldebeken S., Geoffrion M., Spiro W., et al. Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity. Nat. Med. 2014;20:377–384. doi: 10.1038/nm.3467. PubMed DOI PMC

Cochain C., Zernecke A. Macrophages in vascular inflammation and atherosclerosis. Pflügers Arch. 2017;469:485–499. doi: 10.1007/s00424-017-1941-y. PubMed DOI

Lesna I.K., Cejkova S., Kralova A., Fronek J., Petras M., Sekerkova A., Thieme F., Janousek L., Poledne R. Human adipose tissue accumulation is associated with pro-inflammatory changes in subcutaneous rather than visceral adipose tissue. Nutr. Diabetes. 2017;7:e264. doi: 10.1038/nutd.2017.15. PubMed DOI PMC

Kralova Lesna I., Poledne R., Fronek J., Kralova A., Sekerkova A., Thieme F., Pitha J. Macrophage subsets in the adipose tissue could be modified by sex and the reproductive age of women. Atherosclerosis. 2015;241:255–258. doi: 10.1016/j.atherosclerosis.2015.03.018. PubMed DOI

Poledne R., Kralova Lesna I., Kralova A., Fronek J., Cejkova S. The relationship between non-HDL cholesterol and macrophage phenotypes in human adipose tissue. J. Lipid Res. 2016;57:1899–1905. doi: 10.1194/jlr.P068015. PubMed DOI PMC

Min Y., Lowy C., Islam S., Khan F.S., Swaminathan R. Relationship between red cell membrane fatty acids and adipokines in individuals with varying insulin sensitivity. Eur. J. Clin. Nutr. 2011;65:690–695. doi: 10.1038/ejcn.2011.19. PubMed DOI

Muralidharan J., Papandreou C., Sala-Vila A., Rosique-Esteban N., Fito M., Estruch R., Angel Martinez-Gonzalez M., Corella D., Ros E., Razquin C., et al. Fatty Acids Composition of Blood Cell Membranes and Peripheral Inflammation in the PREDIMED Study: A Cross-Sectional Analysis. Nutrients. 2019;11:576. doi: 10.3390/nu11030576. PubMed DOI PMC

Aron-Wisnewsky J., Tordjman J., Poitou C., Darakhshan F., Hugol D., Basdevant A., Aissat A., Guerre-Millo M., Clement K. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J. Clin. Endocrinol. Metab. 2009;94:4619–4623. doi: 10.1210/jc.2009-0925. PubMed DOI

Barros M.H., Hauck F., Dreyer J.H., Kempkes B., Niedobitek G. Macrophage polarisation: An immunohistochemical approach for identifying M1 and M2 macrophages. PLoS ONE. 2013;8:e80908. doi: 10.1371/journal.pone.0080908. PubMed DOI PMC

Kovacikova M., Sengenes C., Kovacova Z., Siklova-Vitkova M., Klimcakova E., Polak J., Rossmeislova L., Bajzova M., Hejnova J., Hnevkovska Z., et al. Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women. Int. J. Obes. 2011;35:91–98. doi: 10.1038/ijo.2010.112. PubMed DOI

Kralova Lesna I., Kralova A., Cejkova S., Fronek J., Petras M., Sekerkova A., Thieme F., Janousek L., Poledne R. Characterisation and comparison of adipose tissue macrophages from human subcutaneous, visceral and perivascular adipose tissue. J. Tansl. Med. 2016;14:208. doi: 10.1186/s12967-016-0962-1. PubMed DOI PMC

Malinska H., Huttl M., Oliyarnyk O., Bratova M., Kazdova L. Conjugated linoleic acid reduces visceral and ectopic lipid accumulation and insulin resistance in chronic severe hypertriacylglycerolemia. Nutrition. 2015;31:1045–1051. doi: 10.1016/j.nut.2015.03.011. PubMed DOI

Eder K. Gas chromatographic analysis of fatty acid methyl esters. J. Chromatogr. B Biomed. Appl. 1995;671:113–131. doi: 10.1016/0378-4347(95)00142-6. PubMed DOI

Menegaut L., Thomas C., Lagrost L., Masson D. Fatty acid metabolism in macrophages: A target in cardio-metabolic diseases. Curr. Opin. Lipidol. 2017;28:19–26. PubMed

Thomas D., Apovian C. Macrophage functions in lean and obese adipose tissue. Metabolism. 2017;72:120–143. doi: 10.1016/j.metabol.2017.04.005. PubMed DOI PMC

Poledne R. Inflammation and atherogenic effects due to saturated fatty acids. In: Watson R.R., De Meester F., editors. Handbook of Lipids in Human Function: Fatty Acids. AOCS Press, Elsevier; Amsterdam, The Netherlands: 2016. pp. 163–179.

Ecker J., Liebisch G., Englmaier M., Grandl M., Robenek H., Schmitz G. Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes. Proc. Natl. Acad. Sci. USA. 2010;107:7817–7822. doi: 10.1073/pnas.0912059107. PubMed DOI PMC

Hodson L., Karpe F. Is there something special about palmitoleate? Curr. Opin. Clin. Nutr. Metab. Care. 2013;16:225–231. doi: 10.1097/MCO.0b013e32835d2edf. PubMed DOI

Afonso M.S., Lavrador M.S., Koike M.K., Cintra D.E., Ferreira F.D., Nunes V.S., Castilho G., Gioielli L.A., Paula Bombo R., Catanozi S., et al. Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation. J. Nutr. Biochem. 2016;32:91–100. doi: 10.1016/j.jnutbio.2016.01.005. PubMed DOI

Knutsen S.F., Fraser G.E., Beeson W.L., Lindsted K.D., Shavlik D.J. Comparison of adipose tissue fatty acids with dietary fatty acids as measured by 24-hour recall and food frequency questionnaire in Black and White Adventists: The Adventist Health Study. Ann. Epidemiol. 2003;13:119–127. doi: 10.1016/S1047-2797(02)00260-0. PubMed DOI

Frigolet M.E., Gutierrez-Aguilar R. The Role of the Novel Lipokine Palmitoleic Acid in Health and Disease. Adv. Nutr. 2017;8:173S–181S. doi: 10.3945/an.115.011130. PubMed DOI PMC

Chan K.L., Pillon N.J., Sivaloganathan D.M., Costford S.R., Liu Z., Theret M., Chazaud B., Klip A. Palmitoleate Reverses High Fat-induced Proinflammatory Macrophage Polarization via AMP-activated Protein Kinase (AMPK) J. Biol. Chem. 2015;290:16979–16988. doi: 10.1074/jbc.M115.646992. PubMed DOI PMC

Foryst-Ludwig A., Kreissl M.C., Benz V., Brix S., Smeir E., Ban Z., Januszewicz E., Salatzki J., Grune J., Schwanstecher A.K., et al. Adipose Tissue Lipolysis Promotes Exercise-induced Cardiac Hypertrophy Involving the Lipokine C16:1n7-Palmitoleate. J. Biol. Chem. 2015;290:23603–23615. doi: 10.1074/jbc.M115.645341. PubMed DOI PMC

Yang Z.H., Pryor M., Noguchi A., Sampson M., Johnson B., Pryor M., Donkor K., Amar M., Remaley A.T. Dietary Palmitoleic Acid Attenuates Atherosclerosis Progression and Hyperlipidemia in Low-Density Lipoprotein Receptor-Deficient Mice. Mol. Nutr. Food Res. 2019;63:e1900120. doi: 10.1002/mnfr.201900120. PubMed DOI PMC

Gong J., Campos H., McGarvey S., Wu Z., Goldberg R., Baylin A. Adipose tissue palmitoleic acid and obesity in humans: Does it behave as a lipokine? Am. J. Clin. Nutr. 2011;93:186–191. doi: 10.3945/ajcn.110.006502. PubMed DOI PMC

Cimen I., Yildirim Z., Dogan A.E., Yildirim A.D., Tufanli O., Onat U.I., Nguyen U., Watkins S.M., Weber C., Erbay E. Double bond configuration of palmitoleate is critical for atheroprotection. Mol. Metab. 2019 doi: 10.1016/j.molmet.2019.08.004. PubMed DOI PMC

De Boer A.A., Monk J.M., Liddle D.M., Power K.A., Ma D.W., Robinson L.E. 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. 2015;2:31. doi: 10.3389/fnut.2015.00031. PubMed DOI PMC

Venkatraman J.T., Toohey T., Clandinin M.T. Does a threshold for the effect of dietary omega-3 fatty acids on the fatty acid composition of nuclear envelope phospholipids exist? Lipids. 1992;27:94–97. doi: 10.1007/BF02535806. PubMed DOI

Calder P.C. Omega-3 fatty acids and inflammatory processes: From molecules to man. Biochem. Soc. Trans. 2017;45:1105–1115. doi: 10.1042/BST20160474. PubMed DOI

Colson C., Ghandour R.A., Dufies O., Rekima S., Loubat A., Munro P., Boyer L., Pisani D.F. Diet Supplementation in omega3 Polyunsaturated Fatty Acid Favors an Anti-Inflammatory Basal Environment in Mouse Adipose Tissue. Nutrients. 2019;11:438. doi: 10.3390/nu11020438. PubMed DOI PMC

Browning L.M., Walker C.G., Mander A.P., West A.L., Madden J., Gambell J.M., Young S., Wang L., Jebb S.A., Calder P.C. Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish. Am. J. Clin. Nutr. 2012;96:748–758. doi: 10.3945/ajcn.112.041343. PubMed DOI PMC

Hagi A., Nakayama M., Shinzaki W., Haji S., Ohyanagi H. Effects of the omega-6: Omega-3 fatty acid ratio of fat emulsions on the fatty acid composition in cell membranes and the anti-inflammatory action. JPEN J. Parenter. Enter. Nutr. 2010;34:263–270. doi: 10.1177/0148607109357625. PubMed DOI

Yaqoob P., Pala H.S., Cortina-Borja M., Newsholme E.A., Calder P.C. Encapsulated fish oil enriched in alpha-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. Eur. J. Clin. Investig. 2000;30:260–274. doi: 10.1046/j.1365-2362.2000.00623.x. PubMed DOI

Manzanares W., Langlois P.L., Dhaliwal R., Lemieux M., Heyland D.K. Intravenous fish oil lipid emulsions in critically ill patients: An updated systematic review and meta-analysis. Crit. Care. 2015;19:167. doi: 10.1186/s13054-015-0888-7. PubMed DOI PMC

Rogacev K.S., Zawada A.M., Emrich I., Seiler S., Bohm M., Fliser D., Woollard K.J., Heine G.H. Lower Apo A-I and lower HDL-C levels are associated with higher intermediate CD14++CD16+ monocyte counts that predict cardiovascular events in chronic kidney disease. Arterioscler. Thromb. Vasc. Biol. 2014;34:2120–2127. doi: 10.1161/ATVBAHA.114.304172. PubMed DOI

Kris-Etherton P.M., Harris W.S., Appel L.J. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747–2757. doi: 10.1161/01.CIR.0000038493.65177.94. PubMed DOI

Wei J., Hou R., Xi Y., Kowalski A., Wang T., Yu Z., Hu Y., Chandrasekar E.K., Sun H., Ali M.K. The association and dose-response relationship between dietary intake of alpha-linolenic acid and risk of CHD: A systematic review and meta-analysis of cohort studies. Br. J. Nutr. 2018;119:83–89. doi: 10.1017/S0007114517003294. PubMed DOI

Camell C., Smith C.W. Dietary oleic acid increases m2 macrophages in the mesenteric adipose tissue. PLoS ONE. 2013;8:e75147. doi: 10.1371/journal.pone.0075147. PubMed DOI PMC

Robblee M.M., Kim C.C., Porter Abate J., Valdearcos M., Sandlund K.L., Shenoy M.K., Volmer R., Iwawaki T., Koliwad S.K. Saturated Fatty Acids Engage an IRE1alpha-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells. Cell Rep. 2016;14:2611–2623. doi: 10.1016/j.celrep.2016.02.053. PubMed DOI PMC

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