Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Non-alcoholic fatty liver disease in obese children and adolescents: a role for nutrition?

European Journal of Clinical Nutrition volume 76, pages 28–39 (2022)Cite this article

Subjects

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in children, paralleling the increasing prevalence of obesity worldwide. The pathogenesis of paediatric NAFLD is not fully understood, but it is known that obesity, nutrition, lifestyle variables, genetic and epigenetic factors may be causally involved in the development of this common metabolic liver disease. In particular, obesity and nutrition are among the strongest risk factors for paediatric NAFLD, which may exert their adverse hepatic effects already before birth. Excess energy intake induces hypertrophy and hyperplasia of adipose tissue with subsequent development of systemic insulin resistance, which is another important risk factor for NAFLD. Diet composition and in particular simple carbohydrate intake (especially high fructose intake) may promote the development of NAFLD, whereas non-digestible carbohydrates (dietary fiber), by affecting gut microbiota, may favour the integrity of gut wall and reduce inflammation, opposing this process. Saturated fat intake may also promote NAFLD development, whereas unsaturated fat intake has some beneficial effects. Protein intake does not seem to affect the development of NAFLD, but further investigation is needed. In conclusion, lifestyle modifications to induce weight loss, through diet and physical activity, remain the mainstay of treatment for paediatric NAFLD. The use of dietary supplements, such as omega-3 fatty acids and probiotics, needs further study before recommendation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Swinburn BA, Kraak VI, Allender S, Atkins VJ, Baker PI, Bogard JR, et al. The global syndemic of obesity, undernutrition, and climate change: the lancet commission report. Lancet. 2019;393:791–846.

    Article  PubMed  Google Scholar 

  2. Valerio G, Maffeis C, Saggese G, Ambruzzi MA, Balsamo A, Bellone S, et al. Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Ital J Pediatr. 2018;44:1–21.

    Article  Google Scholar 

  3. Bentham J, Di Cesare M, Bilano V, Bixby H, Zhou B, Stevens GA, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 2017;390:2627–42.

    Article  Google Scholar 

  4. Simmonds M, Llewellyn A, Owen CG, Woolacott N. Predicting adult obesity from childhood obesity: a systematic review and meta-analysis. Obes Rev. 2016;17:95–107.

    Article  CAS  PubMed  Google Scholar 

  5. Twig G, Yaniv G, Levine H, Leiba A, Goldberger N, Derazne E, et al. Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood. N. Engl J Med. 2016;374:2430–40.

    Article  PubMed  Google Scholar 

  6. Clemente MG, Mandato C, Poeta M, Vajro P. Pediatric non-alcoholic fatty liver disease: recent solutions, unresolved issues, and future research directions. World J Gastroenterol. 2016;22:8078–93.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Di Bonito P, Miraglia del Giudice E, Chiesa C, Licenziati MR, Manco M, Franco F, et al. Preclinical signs of liver and cardiac damage in youth with metabolically healthy obese phenotype. Nutr Metab Cardiovasc Dis. 2018;28:1230–6.

    Article  PubMed  Google Scholar 

  8. Nobili V, Alisi A, Valenti L, Miele L, Feldstein AE, Alkhouri N. NAFLD in children: new genes, new diagnostic modalities and new drugs. Nat Rev Gastroenterol Hepatol. 2019;16:517–30.

    Article  PubMed  Google Scholar 

  9. Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P. The natural history of nonalcoholic fatty liver disease in children: a follow-up study for up to 20-years. Gut 2009;58:1538–44.

    Article  CAS  PubMed  Google Scholar 

  10. Uppal V, Mansoor S, Furuya KN. Pediatric non-alcoholic fatty liver disease. Curr Gastroenterol Rep. 2016;18:1–9.

    Article  Google Scholar 

  11. Younossi Z, Tacke F, Arrese M, Chander Sharma B, Mostafa I, Bugianesi E, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology. 2019;69:2672–82.

    Article  PubMed  Google Scholar 

  12. Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42:641–9.

    Article  PubMed  Google Scholar 

  13. Rudolph B, Bjorklund N, Ovchinsky N, Kogan-Liberman D, Perez A, Liszewski M, et al. Methods to Improve the Noninvasive Diagnosis and Assessment of Disease Severity in Children with Suspected Nonalcoholic Fatty Liver Disease (NAFLD): Study Design. Contemp Clin Trials. 2018;75:51–8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Duncan M, Zong W, Biank VF, Hageman JR. Nonalcoholic fatty liver disease in pediatrics. Pediatr Ann. 2016;45:e54–8.

    Article  PubMed  Google Scholar 

  15. Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, et al. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nu. J Pediatr Gastroenterol Nutr. 2017;64:319–34.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lavine JE, Schwimmer JB, Molleston JP, O. SA, Murray KF, Abrams SH, et al. Treatment of Nonalcoholic Fatty Liver Disease in Children: TONIC Trial Design. Contemp Clin Trials. 2010;31:62–70.

    Article  PubMed  Google Scholar 

  17. Colantonio DA, Kyriakopoulou L, Chan MK, Daly CH, Brinc D, Venner AA, et al. Closing the gaps in pediatric laboratory reference intervals: A caliper database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem. 2012;58:854–68.

    Article  CAS  PubMed  Google Scholar 

  18. Papatheodoridi M, Cholongitas E. Diagnosis of Non-alcoholic Fatty Liver Disease (NAFLD): Current Concepts. Curr Pharm Des. 2019;24:4574–86.

    Article  Google Scholar 

  19. Panera N, Barbaro B, Della Corte C, Mosca A, Nobili V, Alisi A. A review of the pathogenic and therapeutic role of nutrition in pediatric nonalcoholic fatty liver disease. Nutr Res. 2018;58:1–16.

    Article  CAS  PubMed  Google Scholar 

  20. Zusi C, Mantovani A, Olivieri F, Morandi A, Corradi M. Miraglia Del Giudice E, et al. Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents. Dig Liver Dis. 2019;51:1586–92.

  21. Modi N, Murgasova D, Ruager-Martin R, Thomas EL, Hyde MJ, Gale C, et al. The influence of maternal body mass index on infant adiposity and hepatic lipid content. Pediatr Res. 2011;70:287–91.

    Article  PubMed  Google Scholar 

  22. Dayanand NP, Schwimmer JB. The progression and natural history of pediatric nonalcoholic fatty liver disease. Clin Liver Dis. 2016;20:325–38.

    Article  Google Scholar 

  23. Haczeyni F, Bell-Anderson KS, Farrell GC. Causes and mechanisms of adipocyte enlargement and adipose expansion. Obes Rev. 2018;19:406–20.

    Article  CAS  PubMed  Google Scholar 

  24. Canfora EE, Meex RCR, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. 2019;15:261–73.

    Article  CAS  PubMed  Google Scholar 

  25. Rutkowski JM, Stern JH, Scherer PE. The cell biology of fat expansion. J Cell Biol. 2015;208:501–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sbarbati A, Osculati F, Silvagni D, Benati D, Galiè M, Camoglio FS, et al. Obesity and inflammation: evidence for an elementary lesion. Pediatrics. 2006;117:220–3.

    Article  PubMed  Google Scholar 

  27. Kim JI, Huh JY, Sohn JH, Choe SS, Lee YS, Lim CY, et al. Lipid-overloaded enlarged adipocytes provoke insulin resistance independent of inflammation. Mol Cell Biol. 2015;35:1686–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Landgraf K, Rockstroh D, Wagner IV, Weise S, Tauscher R, Schwartze JT, et al. Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children. Diabetes. 2015;64:1249–61.

    Article  CAS  PubMed  Google Scholar 

  29. Skurk T, Alberti-huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007;92:1023–33.

    Article  CAS  PubMed  Google Scholar 

  30. Bugianesi E, Moscatiello S, Ciaravella MF, Marchesini G. Insulin resistance in non-alcoholic fatty liver disease. Curr Pharm Des. 2010;16:1941–51.

    Article  CAS  PubMed  Google Scholar 

  31. Morandi A, Sessa ADI, Zusi C, Umano GR, Mazloum DEL, Fornari E, et al. Nonalcoholic fatty liver disease and estimated insulin resistance in obese youth: a mendelian randomization analysis. J Clin Endocrinol Metab. 2020;105:4046–54.

    Article  Google Scholar 

  32. Gastaldelli A. Insulin resistance and reduced metabolic flexibility: cause or consequence of NAFLD? Clin Sci. 2017;131:2701–5.

    Article  CAS  Google Scholar 

  33. Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62:S47–64.

    Article  PubMed  Google Scholar 

  34. Korenblat KM, Fabbrini E, Mohammed BS, Klein S. Liver, muscle and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects. Gastroenterology. 2008;134:1369–75.

    Article  CAS  PubMed  Google Scholar 

  35. Watt MJ, Miotto PM, De Nardo W, Montgomery MK. The liver as an endocrine organ—linking NAFLD and insulin resistance. Endocr Rev. 2019;40:1367–93.

    Article  PubMed  Google Scholar 

  36. Stefan N, Häring HU. The metabolically benign and malignant fatty liver. Diabetes. 2011;60:2011–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kantartzis K, Peter A, Machicao F, Machann J, Wagner S, Königsrainer I, et al. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes. 2009;58:2616–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mameli C, Mazzantini S, Zuccotti GV. Nutrition in the first 1000 days: the origin of childhood obesity. Int J Environ Res Public Health. 2016;13:1–9.

    Article  Google Scholar 

  39. Maffeis C, Morandi A. Effect of maternal obesity on foetal growth and metabolic health of the offspring. Obes Facts. 2017;10:112–7.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, Webb M, Blendis L, Halpern Z, et al. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): A population based study. J Hepatol. 2007;47:711–7.

    Article  CAS  PubMed  Google Scholar 

  41. Thompson AL. Developmental origins of obesity: early feeding environments, infant growth, and the intestinal microbiome. Am J Hum Biol. 2012;24:350–60.

    Article  PubMed  Google Scholar 

  42. Seki E, Brenner DA, Karin M. A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches. Gastroenterology. 2012;143:307–20.

    Article  CAS  PubMed  Google Scholar 

  43. Nobili V, Schwimmer JB, Vajro P. Breastfeeding and NAFLD from the maternal side of the mother-infant dyad. J Hepatol. 2019;70:13–4.

    Article  PubMed  Google Scholar 

  44. Nobili V, Bedogni G, Alisi A, Pietrobattista A, Alterio A, Tiribelli C, et al. A protective effect of breastfeeding on the progression of non-alcoholic fatty liver disease. Arch Dis Child. 2009;94:801–5.

    Article  CAS  PubMed  Google Scholar 

  45. Chakravarthy MV, Waddell T, Banerjee R, Guess N. Nutrition and nonalcoholic fatty liver disease: current perspectives. Gastroenterol Clin North Am. 2020;49:63–94.

    Article  PubMed  Google Scholar 

  46. Nier A, Brandt A, Conzelmann IB, Özel Y, Bergheim I. Non-alcoholic fatty liver disease in overweight children: role of fructose intake and dietary pattern. Nutrients. 2018;10:1–18.

    Article  Google Scholar 

  47. Mager DR, Iñiguez IR, Gilmour S, Yap J. The effect of a low fructose and low glycemic index/load (FRAGILE) dietary intervention on indices of liver function, cardiometabolic risk factors, and body composition in children and adolescents with nonalcoholic fatty liver disease (NAFLD). J Parenter Enter Nutr. 2015;39:73–84.

    Article  Google Scholar 

  48. Schwarz J, Noworolski SM, Erkin-cakmak A, Korn NJ, Wen MJ, Tai VW, et al. Effects of dietary fructose restriction on liver fat, de novo lipogenesis, and insulin kinetics in children with obesity. Gastroenterology. 2018;153:743–52.

    Article  Google Scholar 

  49. Ludwig DS. Examining the health effects of fructose. JAMA. 2013;310:33–4.

    Article  CAS  PubMed  Google Scholar 

  50. Roncal-Jimenez CA, Lanaspa MA, Rivard CJ, Nakagawa T, Sanchez-Lozada LG, Jalal D, et al. Sucrose induces fatty liver and pancreatic inflammation in male breeder rats independent of excess energy intake. Metabolism. 2011;60:1259–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018;359:1151–6.

    Article  CAS  PubMed  Google Scholar 

  52. Marchesi JR, Adams DH, Fava F, Hermes GDA, Hirsch GM, Hold G, et al. The gut microbiota and host health: a new clinical frontier. Gut. 2016;65:330–9.

    Article  PubMed  Google Scholar 

  53. Charbonneau MR, Donnell DO, Blanton LV, Totten SM, Davis JCC, Barratt MJ, et al. Growth in Models of Infant Undernutrition. Cell. 2016;164:859–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Thompson AL, Monteagudo-Mera A, Cadenas MB, Lampl ML, Azcarate-Peril MA. Milk- and solid-feeding practices and daycare attendance are associated with differences in bacterial diversity, predominant communities, and metabolic and immune function of the infant gut microbiome. Front Cell Infect Microbiol. 2015;5:1–15.

    Article  Google Scholar 

  55. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 2010;107:14691–6.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009;49:1877–87.

    Article  CAS  PubMed  Google Scholar 

  57. Parry SA, Hodson L. Influence of dietary macronutrients on liver fat accumulation and metabolism. J Investig Med. 2017;65:1102–15.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Morandi A, Fornari E, Opri F, Corradi M, Tommasi M, Bonadonna R, et al. High-fat meal, systemic inflammation and glucose homeostasis in obese children and adolescents. Int J Obes. 2017;41:986–9.

    Article  CAS  Google Scholar 

  59. Risérus U. Fatty acids and insulin sensitivity. Curr Opin Clin Nutr Metab Care. 2008;11:100–5.

    Article  PubMed  Google Scholar 

  60. Kaitosaari T, Rönnemaa T, Viikari J, Raitakari O, Arffman M, Marniemi J, et al. Low-saturated fat dietary counseling starting in infancy improves insulin sensitivity in 9-year-old healthy children: The Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) study. Diabetes Care. 2006;29:781–5.

    Article  PubMed  Google Scholar 

  61. Boyraz M, Pirgon O, Dundar B, Cekmez F, Hatipoglu N. Long-term treatment with n-3 polyunsaturated fatty acids as a monotherapy in children with nonalcoholic fatty liver disease. J Clin Res Pediatr Endocrinol. 2015;7:121–7.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Nobili V, Alisi A, Musso G, Scorletti E, Calder PC, Byrne CD. Omega-3 fatty acids: mechanisms of benefit and therapeutic effects in pediatric and adult NAFLD. Crit Rev Clin Lab Sci. 2015;53:106–20.

    Article  PubMed  Google Scholar 

  63. Montagner A, Polizzi A, Fouché E, Ducheix S, Lippi Y, Lasserre F, et al. Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut. 2016;65:1202–14.

    Article  CAS  PubMed  Google Scholar 

  64. Francque S, Verrijken A, Caron S, Prawitt J, Paumelle R, Derudas B, et al. PPARα gene expression correlates with severity and histological treatment response in patients with non-alcoholic steatohepatitis. J Hepatol. 2015;63:164–73.

    Article  CAS  PubMed  Google Scholar 

  65. Elbel EE, Lavine JE, Downes M, Van Natta M, Yu R, Schwimmer JB, et al. Hepatic nuclear receptor expression associates with features of histology in pediatric nonalcoholic fatty liver disease. Hepatol Commun. 2018;2:1213–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Markova M, Pivovarova O, Hornemann S, Sucher S, Frahnow T, Wegner K, et al. Isocaloric diets high in animal or plant protein reduce liver fat and inflammation in individuals with type 2 diabetes. Gastroenterology. 2016;152:571–85.e8.

    Article  PubMed  Google Scholar 

  67. Bortolotti M, Kreis R, Debard C, Cariou B, Faeh D, Chetiveaux M, et al. High protein intake reduces intrahepatocellular lipid deposition in humans. Am J Clin Nutr. 2009;90:1002–10.

    Article  CAS  PubMed  Google Scholar 

  68. Wehmeyer MH, Zyriax BC, Jagemann B, Roth E, Windler E. JS Zur W, et al. Nonalcoholic fatty liver disease is associated with excessive calorie intake rather than a distinctive dietary pattern. Medicine. 2016;95:e3887.

  69. Jiao N, Baker SS, Chapa-Rodriguez A, Liu W, Nugent CA, Tsompana M, et al. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD. Gut 2017;0:1–11.

    Google Scholar 

  70. Arab JP, Karpen SJ, Dawson PA, Arrese M, Trauner M. Bile acids and nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives. Hepatology. 2017;65:350–62.

    Article  PubMed  Google Scholar 

  71. McGlone ER, Bloom SR. Bile acids and the metabolic syndrome. Ann Clin Biochem. 2019;56:1–31.

    Article  Google Scholar 

  72. Rodríguez-Morató J, Matthan NR. Nutrition and gastrointestinal microbiota, microbial-derived secondary bile acids, and cardiovascular disease. Curr Atheroscler Rep. 2020;22:1–12.

    Article  Google Scholar 

  73. Trefflich I, Marschall HU, Di Giuseppe R, Ståhlman M, Michalsen A, Lampen A, et al. Associations between dietary patterns and bile acids—results from a cross-sectional study in vegans and omnivores. Nutrients. 2020;12:1–14.

    Google Scholar 

  74. Li T, Chiang JYL. Bile acid signaling in metabolic disease and drug therapy. Pharm Rev. 2014;66:948–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ridlon JM, Joong Kang D, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol. 2014;30:332–8.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Africa JA, Newton KP, Schwimmer JB. Lifestyle interventions including nutrition, exercise, and supplements for nonalcoholic fatty liver disease in children. Dig Dis Sci. 2016;61:1375–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Grønbæk H, Lange A, Birkebæk NH, Holland-Fischer P, Solvig J, Hørlyck A, et al. Effect of a 10-week weight loss camp on fatty liver disease and insulin sensitivity in obese danish children. J Pediatr Gastroenterol Nutr. 2012;54:223–8.

    Article  PubMed  Google Scholar 

  78. Campos RMS, De Piano A, Da Silva PL, Carnier J, Sanches PL, Corgosinho FC, et al. The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: Effects of long-term interdisciplinary therapy. Endocrine. 2012;42:146–56.

    Article  CAS  PubMed  Google Scholar 

  79. Sekkarie A, Welsh JA, Vos MB. Carbohydrates and diet patterns in nonalcoholic fatty liver disease in children and adolescents. Curr Opin Clin Nutr Metab Care. 2018;21:1–6.

    Article  Google Scholar 

  80. Della Corte C, Mosca A, Vania A, Alterio A, Iasevoli S, Nobili V. Good adherence to the Mediterranean diet reduces the risk for NASH and diabetes in pediatric patients with obesity: The results of an Italian Study. Nutrition. 2017;39–40:8–14.

    Article  PubMed  Google Scholar 

  81. Ramon-Krauel M, Salsberg SL, Ebbeling CB, Voss SD, Mulkern RV, Apura MM, et al. A low-glycemic-load versus low-fat diet in the treatment of fatty liver in obese children. Child Obes. 2013;9:252–60.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Jin R, Welsh JA, Le NA, Holzberg J, Sharma P, Martin DR, et al. Dietary fructose reduction improves markers of cardiovascular disease risk in Hispanic-American adolescents with NAFLD. Nutrients. 2014;6:3187–201.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Nobili V, Bedogni G, Alisi A, Pietrobattista A, Risé P, Galli C, et al. Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: Double-blind randomised controlled clinical trial. Arch Dis Child. 2011;96:350–3.

    Article  PubMed  Google Scholar 

  84. Janczyk W, Lebensztejn D, Wierzbicka-Rucińska A, Mazur A, Neuhoff-Murawska J, Matusik P, et al. Omega-3 fatty acids therapy in children with nonalcoholic fatty liver disease: a randomized controlled trial. J Pediatr. 2015;166:1358–1363.e3.

    Article  CAS  PubMed  Google Scholar 

  85. Houringan SK, Abrams S, Yates K, Pfeifer K, Torbenson M, Murray K, et al. The relationship between vitamin D status and non-alcoholic fatty liver disease in children. J Pediatr Gastroenterol Nutr. 2015;60:396–404.

    Article  Google Scholar 

  86. Kitson MT, Pham A, Gordon A, Kemp W, Roberts SK. High-dose vitamin D supplementation and liver histology in NASH. Gut. 2016;65:717–8.

    Article  CAS  PubMed  Google Scholar 

  87. Corte CD, Carpino G, De Vito R, et al. Docosahexanoic acid plus vitamin D treatment improves features of NAFLD in children with serum vitamin D deficiency: results from a single centre trial. PLoS One. 2016;11:1–17.

    Google Scholar 

  88. Janczyk W, Socha P, Lebensztejn D, Wierzbicka A, Mazur A, Neuhoff-Murawska J, et al. Omega-3 fatty acids for treatment of non-alcoholic fatty liver disease: design and rationale of randomized controlled trial. BMC Pediatr. 2013;13:1–11.

    Article  Google Scholar 

  89. Ma YY, Li L, Yu CH, Shen Z, Chen LH, Li YM. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol. 2013;19:6911–8.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Vajro P, Mandato C, Licenziati MR, Franzese A, Vitale DF, Lenta S, et al. Effects of lactobacillus rhamnosus strain gg in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr. 2011;52:740–3.

    Article  PubMed  Google Scholar 

  91. Famouri F, Shariat Z, Hashemipour M, Keikha M, Kelishadi R. Effects of probiotics on nonalcoholic fatty liver disease in obese children and adolescents. J Pediatr Gastroenterol Nutr. 2017;64:413–7.

    Article  CAS  PubMed  Google Scholar 

  92. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl J Med. 2010;362:1675–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, et al. Effect of vitamin e or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents the tonic randomized controlled trial. JAMA. 2011;305:1659–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Foster C, Moore JB, Singletary CR, Skelton JA. Physical activity and family-based obesity treatment: a review of expert recommendations on physical activity in youth. Clin Obes. 2018;8:68–79.

    Article  CAS  PubMed  Google Scholar 

  95. Nobili V, Marcellini M, Devito R, Ciampalini P, Piemonte F, Comparcola D, et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology. 2006;44:458–65.

    Article  PubMed  Google Scholar 

  96. Pozzato C, Verduci E, Scaglioni S, Radaelli G, Salvioni M, Rovere A, et al. Liver fat change in obese children after a 1-year nutrition-behavior intervention. J Pediatr Gastroenterol Nutr. 2010;51:331–5.

    Article  CAS  PubMed  Google Scholar 

  97. Bacchi E, Negri C, Targher G, Faccioli N, Lanza M, Zoppini G, et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 randomized trial). Hepatology. 2013;58:1287–95.

    Article  CAS  PubMed  Google Scholar 

  98. Hashida R, Kawaguchi T, Bekki M, Omoto M, Matsuse H, Nago T, et al. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: a systematic review. J Hepatol. 2017;66:142–52.

    Article  PubMed  Google Scholar 

  99. Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67:829–46.

    Article  PubMed  Google Scholar 

  100. Thyfault JP. Scott Rector R. Exercise combats hepatic steatosis: Potential mechanisms and clinical implications. Diabetes. 2020;69:517–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Lee SJ, Bacha F, Hannon T, Kuk JL, Boesch C, Arslanian S. Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys a randomized, controlled trial. Diabetes. 2012;61:2787–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. González-Ruiz K, Ramírez-Vélez R, Correa-Bautista JE, Peterson MD, García-Hermoso A. The effects of exercise on abdominal fat and liver enzymes in pediatric obesity: a systematic review and meta-analysis. Child Obes. 2017;13:272–82.

    Article  PubMed  Google Scholar 

  103. Kantartzis K, Thamer C, Peter A, Machann J, Schick F, Schraml C, et al. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut. 2009;58:1281–8.

    Article  CAS  PubMed  Google Scholar 

  104. Johnson NA, Sachinwalla T, Walton DW, Smith K, Armstrong A, Thompson MW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009;50:1105–12.

    Article  CAS  PubMed  Google Scholar 

  105. Meissner M, Lombardo E, Havinga R, Tietge UJF, Kuipers F, Groen AK. Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice. Atherosclerosis. 2011;218:323–9.

    Article  CAS  PubMed  Google Scholar 

  106. Van Der Windt DJ, Sud V, Zhang H, Tsung A, Huang H. The effects of physical exercise on fatty liver disease. Gene Expr. 2018;18:89–101.

    Article  PubMed  PubMed Central  Google Scholar 

  107. WHO. Evidence on physical activity and sedentary behaviour for children and adolescents (5 to under 18 years of age). In: Who Guidelines on Physical Activity. Geneva: World Health Organization; 2020. p. 8–98.

  108. Nobili V, Vajro P, Dezsofi A, Fischler B, Hadzic N, Jahnel J, et al. Indications and limitations of bariatric intervention in severely obese children and adolescents with and without nonalcoholic steatohepatitis: ESPGHAN hepatology committee position statement. J Pediatr Gastroenterol Nutr. 2015;60:550–61.

    Article  PubMed  Google Scholar 

  109. Bower G, Toma T, Harling L, Jiao LR, Efthimiou E, Darzi A, et al. Bariatric surgery and non-alcoholic fatty liver disease: a systematic review of liver biochemistry and histology. Obes Surg. 2015;25:2280–9.

    Article  PubMed  Google Scholar 

  110. Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149:379–88.

    Article  PubMed  Google Scholar 

  111. Rudolph A, Hilbert A. Post-operative behavioural management in bariatric surgery: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2013;14:292–302.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgical Sciences, Dentistry, Paediatrics and Gynaecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    Luisa Bonsembiante & Claudio Maffeis

  2. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    Giovanni Targher

Authors
  1. Luisa Bonsembiante
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovanni Targher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claudio Maffeis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudio Maffeis.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bonsembiante, L., Targher, G. & Maffeis, C. Non-alcoholic fatty liver disease in obese children and adolescents: a role for nutrition?. Eur J Clin Nutr 76, 28–39 (2022). https://doi.org/10.1038/s41430-021-00928-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-021-00928-z

Search

Advanced search

Quick links