Abstract
Aim
Our aim is to demonstrate that a healthy diet might reduce the relation between adiposity and inflammation, whereas an unhealthy diet may increase the effect of adiposity on inflammatory biomarkers.
Methods
In 618 adolescents (13–17 years) of the European HELENA study, data were available on body composition, a set of inflammation markers, and food intake determined by a self-administered computerized 24-h recall. A 9-point Mediterranean diet score and an antioxidant-rich diet score were used as dietary parameters and tested as moderator. Total body fat was represented by the sum of six skinfold thicknesses and central adiposity by waist circumference. A set of inflammation-related biomarkers was used as outcome: a pro/anti-inflammatory interleukins ratio, TGFβ-1, C-reactive protein, TNF-α, 3 cell adhesion molecules, and 3 types of immune cells; gamma-glutamyltransferase (GGT) and homocysteine were used as cardiovascular disease risk biomarkers, and alanine transaminase (ALT) as liver dysfunction biomarker. Multiple linear regression analyses tested moderation by diet in the adiposity-inflammation association and were adjusted for age, sex, country, puberty, socioeconomic status.
Results
Both the Mediterranean and antioxidant-rich diet, and overall and central adiposity, were important in the moderation. Diet was a significant protective moderator in the effect of adiposity on the pro/anti-inflammatory interleukins ratio, TGFβ-1, GGT, and ALT.
Conclusion
In conclusion, in some cases, a diet rich in antioxidants and essential nutrients may attenuate the concentration of inflammatory biomarkers caused by adiposity, whereas a poor diet appears to contribute to the onset of early oxidative stress signs.
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References
(2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 894:i–xii, 1–253
Moreno LA, Kersting M, de Henauw S, González-Gross M, Sichert-Hellert W, Matthys C, Mesana MI, Ross N (2005) How to measure dietary intake and food habits in adolescence: the European perspective. Int J Obes (Lond) 29(Suppl 2):S66–S77
Calder PC, Ahluwalia N, Brouns F, Buetler T, Clement K, Cunningham K, Esposito K, Jönsson LS, Kolb H, Lansink M, Marcos A, Margioris A, Matusheski N, Nordmann H, O’Brien J, Pugliese G, Rizkalla S, Schalkwijk C, Tuomilehto J, Wärnberg J, Watzl B, Winklhofer-Roob BM (2011) Dietary factors and low-grade inflammation in relation to overweight and obesity. Br J Nutr 106(Suppl 3):S5–S78. https://doi.org/10.1017/S0007114511005460
Calder PC (1997) n-3 polyunsaturated fatty acids and cytokine production in health and disease. Ann Nutr Metab 41(4):203–234
Ferrari M, Cuenca-García M, Valtueña J, Moreno LA, Censi L, González-Gross M, Androutsos O, Gilbert CC, Huybrechts I, Dallongeville J, Sjöström M, Molnar D, De Henauw S, Gómez-Martínez S, de Moraes AC, Kafatos A, Widhalm K, Leclercq C, Group HS (2015) Inflammation profile in overweight/obese adolescents in Europe: an analysis in relation to iron status. Eur J Clin Nutr 69(2):247–255. https://doi.org/10.1038/ejcn.2014.154
Steene-Johannessen J, Kolle E, Reseland JE, Anderssen SA, Andersen LB (2010) Waist circumference is related to low-grade inflammation in youth. Int J Pediatr Obes 5(4):313–319. https://doi.org/10.3109/17477160903497035
Galcheva SV, Iotova VM, Yotov YT, Bernasconi S, Street ME (2011) Circulating proinflammatory peptides related to abdominal adiposity and cardiometabolic risk factors in healthy prepubertal children. Eur J Endocrinol 164(4):553–558. https://doi.org/10.1530/EJE-10-1124
O’Keefe JH, Gheewala NM, O’Keefe JO (2008) Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health. J Am Coll Cardiol 51(3):249–255. https://doi.org/10.1016/j.jacc.2007.10.016
Navarro E, Funtikova AN, Fíto M, Schröder H (2015) Can metabolically healthy obesity be explained by diet, genetics, and inflammation? Mol Nutr Food Res 59(1):75–93. https://doi.org/10.1002/mnfr.201400521
Connaughton RM, McMorrow AM, McGillicuddy FC, Lithander FE, Roche HM (2016) Impact of anti-inflammatory nutrients on obesity-associated metabolic-inflammation from childhood through to adulthood. Proc Nutr Soc 75(2):115–124. https://doi.org/10.1017/S0029665116000070
Chrysohoou C, Panagiotakos DB, Pitsavos C, Das UN, Stefanadis C (2004) Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the ATTICA Study. J Am Coll Cardiol 44(1):152–158. https://doi.org/10.1016/j.jacc.2004.03.039
Casas R, Sacanella E, Estruch R (2014) The immune protective effect of the Mediterranean diet against chronic low-grade inflammatory diseases. Endocr Metab Immune Disord Drug Targets 14(4):245–254
Schwingshackl L, Hoffmann G (2014) Mediterranean dietary pattern, inflammation and endothelial function: a systematic review and meta-analysis of intervention trials. Nutr Metab Cardiovasc Dis 24(9):929–939. https://doi.org/10.1016/j.numecd.2014.03.003
Bonaccio M, Cerletti C, Iacoviello L, de Gaetano G (2015) Mediterranean diet and low-grade subclinical inflammation: the Moli-sani study. Endocr Metab Immune Disord Drug Targets 15(1):18–24
Root MM, McGinn MC, Nieman DC, Henson DA, Heinz SA, Shanely RA, Knab AM, Jin F (2012) Combined fruit and vegetable intake is correlated with improved inflammatory and oxidant status from a cross-sectional study in a community setting. Nutrients 4(1):29–41. https://doi.org/10.3390/nu4010029
Shivappa N, Hébert JR, Rietzschel ER, De Buyzere ML, Langlois M, Debruyne E, Marcos A, Huybrechts I (2015) Associations between dietary inflammatory index and inflammatory markers in the Asklepios Study. Br J Nutr 113(4):665–671. https://doi.org/10.1017/S000711451400395X
Lambert M, Delvin EE, Paradis G, O’Loughlin J, Hanley JA, Levy E (2004) C-reactive protein and features of the metabolic syndrome in a population-based sample of children and adolescents. Clin Chem 50(10):1762–1768. https://doi.org/10.1373/clinchem.2004.036418
McCrindle BW (2015) Cardiovascular consequences of childhood obesity. Can J Cardiol 31(2):124–130. https://doi.org/10.1016/j.cjca.2014.08.017
Moreno LA, De Henauw S, González-Gross M, Kersting M, Molnár D, Gottrand F, Barrios L, Sjöström M, Manios Y, Gilbert CC, Leclercq C, Widhalm K, Kafatos A, Marcos A, Group HS (2008) Design and implementation of the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Int J Obes (Lond) 32(Suppl 5):S4–S11. https://doi.org/10.1038/ijo.2008.177
Diethelm K, Huybrechts I, Moreno L, De Henauw S, Manios Y, Beghin L, González-Gross M, Le Donne C, Cuenca-García M, Castillo MJ, Widhalm K, Patterson E, Kersting M (2014) Nutrient intake of European adolescents: results of the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Public Health Nutr 17(3):486–497. https://doi.org/10.1017/S1368980013000463
Vereecken CA, Covents M, Matthys C, Maes L (2005) Young adolescents’ nutrition assessment on computer (YANA-C). Eur J Clin Nutr 59(5):658–667. https://doi.org/10.1038/sj.ejcn.1602124
Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, Gnardellis C, Lagiou P, Polychronopoulos E, Vassilakou T, Lipworth L, Trichopoulos D (1995) Diet and overall survival in elderly people. BMJ 311(7018):1457–1460
Trichopoulou A, Costacou T, Bamia C, Trichopoulos D (2003) Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 348(26):2599–2608. https://doi.org/10.1056/NEJMoa025039
Trichopoulou A (2004) Traditional Mediterranean diet and longevity in the elderly: a review. Public Health Nutr 7(7):943–947
Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320(7244):1240–1243
Nagy E, Vicente-Rodriguez G, Manios Y, Béghin L, Iliescu C, Censi L, Dietrich S, Ortega FB, De Vriendt T, Plada M, Moreno LA, Molnar D, Group HS (2008) Harmonization process and reliability assessment of anthropometric measurements in a multicenter study in adolescents. Int J Obes (Lond) 32(Suppl 5):S58–S65. https://doi.org/10.1038/ijo.2008.184
Tanner JM, Whitehouse RH (1976) Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 51(3):170–179
González-Gross M, Breidenassel C, Gómez-Martínez S, Ferrari M, Béghin L, Spinneker A, Díaz LE, Maiani G, Demailly A, Al-Tahan J, Albers U, Wärnberg J, Stoffel-Wagner B, Jiménez-Pavón D, Libersa C, Pietrzik K, Marcos A, Stehle P (2008) Sampling and processing of fresh blood samples within a European multicenter nutritional study: evaluation of biomarker stability during transport and storage. Int J Obes (Lond) 32(Suppl 5):S66–S75. https://doi.org/10.1038/ijo.2008.185
Minihane AM, Vinoy S, Russell WR, Baka A, Roche HM, Tuohy KM, Teeling JL, Blaak EE, Fenech M, Vauzour D, McArdle HJ, Kremer BH, Sterkman L, Vafeiadou K, Benedetti MM, Williams CM, Calder PC (2015) Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr 114(7):999–1012. https://doi.org/10.1017/S0007114515002093
Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, Klunker S, Meyer N, O’Mahony L, Palomares O, Rhyner C, Ouaked N, Quaked N, Schaffartzik A, Van De Veen W, Zeller S, Zimmermann M, Akdis CA (2011) Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. J Allergy Clin Immunol 127(3):701–721.e701–770. https://doi.org/10.1016/j.jaci.2010.11.050
Targher G (2010) Elevated serum gamma-glutamyltransferase activity is associated with increased risk of mortality, incident type 2 diabetes, cardiovascular events, chronic kidney disease and cancer—a narrative review. Clin Chem Lab Med 48(2):147–157. https://doi.org/10.1515/CCLM.2010.031
Fraser A, Longnecker MP, Lawlor DA (2007) Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999–2004. Gastroenterology 133(6):1814–1820. https://doi.org/10.1053/j.gastro.2007.08.077
Martinez-Gomez D, Ortega FB, Ruiz JR, Vicente-Rodriguez G, Veiga OL, Widhalm K, Manios Y, Béghin L, Valtueña J, Kafatos A, Molnar D, Moreno LA, Marcos A, Castillo MJ, Sjöström M, Group Hs (2011) Excessive sedentary time and low cardiorespiratory fitness in European adolescents: the HELENA study. Arch Dis Child 96(3):240–246. https://doi.org/10.1136/adc.2010.187161
Vanhelst J, Béghin L, Turck D, Gottrand F (2011) New validated thresholds for various intensities of physical activity in adolescents using the Actigraph accelerometer. Int J Rehabil Res 34(2):175–177. https://doi.org/10.1097/MRR.0b013e328340129e
Jiménez Pavón D, Ortega FP, Ruiz JR, España Romero V, García Artero E, Moliner Urdiales D, Gómez Martínez S, Vicente Rodríguez G, Manios Y, Béghin L, Répasy J, Sjöstrom M, Moreno LA, González Gross M, Castillo MJ, Group HS (2010) Socioeconomic status influences physical fitness in European adolescents independently of body fat and physical activity: the HELENA study. Nutr Hosp 25(2):311–316
Hayes AF, Rockwood NJ (2016) Regression-based statistical mediation and moderation analysis in clinical research: observations, recommendations, and implementation. Behav Res Ther. https://doi.org/10.1016/j.brat.2016.11.001
Hayes A (2013) Introduction to mediation, moderation, and conditional process analysis: a regression-based approach. Guilford Publications, New York. ISBN 978-1-60918-230-4
Dai J, Miller AH, Bremner JD, Goldberg J, Jones L, Shallenberger L, Buckham R, Murrah NV, Veledar E, Wilson PW, Vaccarino V (2008) Adherence to the mediterranean diet is inversely associated with circulating interleukin-6 among middle-aged men: a twin study. Circulation 117(2):169–175. https://doi.org/10.1161/CIRCULATIONAHA.107.710699
Hoebeeck LI, Rietzschel ER, Langlois M, De Buyzere M, De Bacquer D, De Backer G, Maes L, Gillebert T, Huybrechts I (2011) The relationship between diet and subclinical atherosclerosis: results from the Asklepios Study. Eur J Clin Nutr 65(5):606–613. https://doi.org/10.1038/ejcn.2010.286
Dinarello CA (1997) Proinflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock. Chest 112(6 Suppl):321S–329S
Calder PC (1998) Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids. Braz J Med Biol Res 31(4):467–490
Giugliano D, Ceriello A, Esposito K (2006) The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol 48(4):677–685. https://doi.org/10.1016/j.jacc.2006.03.052
Kiecolt-Glaser JK (2010) Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge. Psychosom Med 72(4):365–369. https://doi.org/10.1097/PSY.0b013e3181dbf489
Border WA, Ruoslahti E (1992) Transforming growth factor-beta in disease: the dark side of tissue repair. J Clin Invest 90(1):1–7. https://doi.org/10.1172/JCI115821
Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A (2001) Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther 15(10):1667–1672
Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A, Basdevant A, Guerre-Millo M, Poitou C, Zucker JD, Bedossa P, Clément K (2010) Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 59(11):2817–2825. https://doi.org/10.2337/db10-0585
Reggio S, Rouault C, Poitou C, Bichet JC, Prifti E, Bouillot JL, Rizkalla S, Lacasa D, Tordjman J, Clément K (2016) Increased basement membrane components in adipose tissue during obesity: links with TGFβ and metabolic phenotypes. J Clin Endocrinol Metab 101(6):2578–2587. https://doi.org/10.1210/jc.2015-4304
Parola M, Muraca R, Dianzani I, Barrera G, Leonarduzzi G, Bendinelli P, Piccoletti R, Poli G (1992) Vitamin E dietary supplementation inhibits transforming growth factor beta 1 gene expression in the rat liver. FEBS Lett 308(3):267–270
Koenig G, Seneff S (2015) Gamma-glutamyltransferase: a predictive biomarker of cellular antioxidant inadequacy and disease risk. Dis Markers 2015:818570. https://doi.org/10.1155/2015/818570
Lee DH, Blomhoff R, Jacobs DR (2004) Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radic Res 38(6):535–539
Kunutsor SK (2016) Gamma-glutamyltransferase-friend or foe within? Liver Int 36(12):1723–1734. https://doi.org/10.1111/liv.13221
Whitfield JB (2001) Gamma glutamyl transferase. Crit Rev Clin Lab Sci 38(4):263–355. https://doi.org/10.1080/20014091084227
Mason JE, Starke RD, Van Kirk JE (2010) Gamma-glutamyl transferase: a novel cardiovascular risk biomarker. Prev Cardiol 13(1):36–41. https://doi.org/10.1111/j.1751-7141.2009.00054.x
Yamada J, Tomiyama H, Yambe M, Koji Y, Motobe K, Shiina K, Yamamoto Y, Yamashina A (2006) Elevated serum levels of alanine aminotransferase and gamma glutamyltransferase are markers of inflammation and oxidative stress independent of the metabolic syndrome. Atherosclerosis 189(1):198–205. https://doi.org/10.1016/j.atherosclerosis.2005.11.036
Whitfield JB (2007) Serum gamma-glutamyltransferase and risk of disease. Clin Chem 53(1):1–2. https://doi.org/10.1373/clinchem.2006.080911
Wiegand S, Keller KM, Röbl M, L’Allemand D, Reinehr T, Widhalm K, Holl RW, Adipositas A-SGatGCN (2010) Obese boys at increased risk for nonalcoholic liver disease: evaluation of 16,390 overweight or obese children and adolescents. Int J Obes (Lond) 34(10):1468–1474. https://doi.org/10.1038/ijo.2010.106
Marzuillo P, Grandone A, Perrone L, Miraglia Del Giudice E (2015) Understanding the pathophysiological mechanisms in the pediatric non-alcoholic fatty liver disease: The role of genetics. World J Hepatol 7(11):1439–1443. https://doi.org/10.4254/wjh.v7.i11.1439
Ahn MB, Bae WR, Han KD, Cho WK, Cho KS, Park SH, Jung MH, Suh BK (2015) Association between serum alanine aminotransferase level and obesity indices in Korean adolescents. Korean J Pediatr 58(5):165–171. https://doi.org/10.3345/kjp.2015.58.5.165
Kim WR, Flamm SL, Di Bisceglie AM, Bodenheimer HC, Disease PPCotAAftSoL (2008) Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 47(4):1363–1370. https://doi.org/10.1002/hep.22109
Boyraz M, Pirgon Ö, Dündar B, Çekmez F, Hatipoğlu N (2015) Long-term treatment with n-3 polyunsaturated fatty acids as a monotherapy in children with nonalcoholic fatty liver disease. J Clin Res Pediatr Endocrinol 7(2):121–127. https://doi.org/10.4274/jcrpe.1749
Zhu FS, Liu S, Chen XM, Huang ZG, Zhang DW (2008) Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia. World J Gastroenterol 14(41):6395–6400
Nobili V, Bedogni G, Alisi A, Pietrobattista A, Risé P, Galli C, Agostoni C (2011) Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial. Arch Dis Child 96(4):350–353. https://doi.org/10.1136/adc.2010.192401
Rodríguez G, Moreno LA, Blay MG, Blay VA, Fleta J, Sarría A, Bueno M, Group A-ZS (2005) Body fat measurement in adolescents: comparison of skinfold thickness equations with dual-energy X-ray absorptiometry. Eur J Clin Nutr 59(10):1158–1166. https://doi.org/10.1038/sj.ejcn.1602226
Sarría A, García-Llop LA, Moreno LA, Fleta J, Morellón MP, Bueno M (1998) Skinfold thickness measurements are better predictors of body fat percentage than body mass index in male Spanish children and adolescents. Eur J Clin Nutr 52(8):573–576
Acknowledgements
The HELENA Study was carried out with the financial support of the European Community Sixth RTD Framework Programme (Contract FOODCT-2005-007034). The writing group takes sole responsibility for the content of this article. The European Community is not liable for any use that may be made of the information contained therein.
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AA formulated the research question, has analyzed the data and wrote a draft of the paper. NM helped in formulating the research question, analyzing the data and did editing of the first draft. NM and SDH are co-supervisor and supervisor of Aline Arouca; LAM was coordinator of the HELENA project. All other authors were involved in the HELENA project (coordinator or data collection). AM was responsible for the inflammatory parameter analyses. IH developed the Mediterranean diet score. MGG was responsible for the complete blood sampling and collection. All authors have read the draft and agreed on the final version. The authors would like to thank Anke Carstensen and Petra Pickert for their contribution to the laboratory work.
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Arouca, A., Moreno, L.A., Gonzalez-Gil, E.M. et al. Diet as moderator in the association of adiposity with inflammatory biomarkers among adolescents in the HELENA study. Eur J Nutr 58, 1947–1960 (2019). https://doi.org/10.1007/s00394-018-1749-3
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DOI: https://doi.org/10.1007/s00394-018-1749-3