Skip to main content
SpringerLink
Log in

Pro- and anti-inflammatory cytokines are the game-changers in childhood obesity-associated metabolic disorders (diabetes and non-alcoholic fatty liver diseases)

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

IL-1:

Interleukin-1

IL-2:

Interleukin-2

IL-3:

Interleukin-3

IL-4:

Interleukin-4

IL-5:

Interleukin-5

IL-6:

Interleukin-6

IL-7:

Interleukin-7

IL-8:

Interleukin-8

IL-9:

Interleukin-9

IL-10:

Interleukin-10

IL-11:

Interleukin-11

IL-12:

Interleukin-12

IL-13:

Interleukin-13

IL-14:

Interleukin-14

IL-15:

Interleukin-15

IL-16:

Interleukin-16

IL-17:

Interleukin-17

IL-18:

Interleukin-18

IL-21:

Interleukin-21

IL-23:

Interleukin-23

GM-CSF:

Granulocyte-Macrophage Colony-Stimulating Factor

MIG:

Monokine Induced by Gamma

IP-10:

Interferon Gamma-Induced Protein 1

TGF-1β:

Transforming Growth Factor -I beta

TNF-α:

Tumor Necrosis Factor-Alpha

IFN-γ:

Interferon-Gamma

LDL:

Low-Density Lipoproteins

HDL:

High-Density Lipoproteins

MCP-1:

Monocyte Chemoattractant Protein-1

AST:

Aspartate Aminotransferase

ALT:

Alanine Transaminase

JAK/STAT3:

Janus Kinase/Signal Transducers and Activators of Transcription 3

HOMA-IR:

Homeostatic Model Assessment for Insulin Resistance

TNFSF:

Tumor Necrosis Factor Superfamily

PDFF:

Proton Density Fat-Fraction

TG:

Triglycerides

GDF15:

Growth Differentiation Factor 15

References

  1. Collaboration NRF. 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 

  2. World Health Organization. Draft recommendations for the prevention and management of obesity over the life course, including potential targets. 2021.

  3. Lange SJ, Kompaniyets L, Freedman DS, Kraus EM, Porter R, et al. Longitudinal trends in Body Mass Index before and during the COVID-19 pandemic among persons aged 2–19 years — United States, 2018–2020. MMWR Morb Mortal Wkly Rep. 2021;70:1278–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ling J, Chen S, Zahry NR, Kao TSA. Economic burden of childhood overweight and obesity: a systematic review and meta-analysis. Obes Rev. 2023;24:e13535.

    Article  PubMed  Google Scholar 

  5. Carsley S, Tu K, Parkin PC, Pullenayegum E, Birken CS. Overweight and obesity in preschool aged children and risk of mental health service utilization. Int J Obes. 2019;43:1325–33.

    Article  Google Scholar 

  6. Mamrot P, Hanć T. The association of the executive functions with overweight and obesity indicators in children and adolescents: a literature review. Neurosci Biobehav Rev. 2019;107:59–68.

    Article  PubMed  Google Scholar 

  7. Davies S. Time to Solve Childhood Obesity: An Independent Report by the Chief Medical Officer. 2019.

  8. Duan Y, Luo J, Pan X, Wei J, Xiao X, Li J, et al. Association between inflammatory markers and non-alcoholic fatty liver disease in obese children. Front Public Heal. 2022;10:991393.

    Article  Google Scholar 

  9. Tagi VM, Giannini C, Chiarelli F. Insulin resistance in children. Front Endocrinol (Lausanne). 2019;10:1–13.

    Article  Google Scholar 

  10. Chait A, den Hartigh LJ. Adipose tissue distribution, inflammation and its metabolic consequences, including Diabetes and Cardiovascular Disease. Front Cardiovasc Med. 2020;7:1–41.

    Article  Google Scholar 

  11. Powell-Wiley TM, Poirier P, Burke LE, Després JP, Gordon-Larsen P, Lavie CJ, et al. Obesity and Cardiovascular Disease A Scientific Statement from the American Heart Association. Circulation. 2021;143:E984–1010.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Yang F, Dawes P, Leroi I, Gannon B. Measurement tools of resource use and quality of life in clinical trials for dementia or cognitive impairment interventions: a systematically conducted narrative review. Int J Geriatr Psychiatry. 2018;33:e166–76.

    Article  PubMed  Google Scholar 

  13. Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA, Liu G. Cytokines: from clinical significance to quantification. Adv Sci. 2021;8:2004433.

    Article  CAS  Google Scholar 

  14. Marshall JS, Warrington R, Watson W, Kim HL. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol. 2018;14:49.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 cytokine storm; what we know so far. Front Immunol. 2020;11:1–4.

    Article  Google Scholar 

  16. Amere Subbarao S. Cancer vs. SARS-CoV-2 induced inflammation, overlapping functions, and pharmacological targeting. Inflammopharmacology. 2021;29:343–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bhasin E, Mishra S, Pathak G, Chauhan PS, Kulshreshtha A. Cytokine database of stress and metabolic disorders (CdoSM): a connecting link between stress and cardiovascular disease, hypertension, diabetes and obesity. 3 Biotech. 2022;12:1–12.

    Article  Google Scholar 

  18. Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019;20:6008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wautier JL, Wautier MP. Pro- and anti-inflammatory prostaglandins and cytokines in humans: a Mini Review. Int J Mol Sci. 2023;24:9647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mărginean CO, Meliţ LE, Huțanu A, Ghiga DV, Săsăran MO. The adipokines and inflammatory status in the era of pediatric obesity. Cytokine. 2020;126:4–9.

    Article  Google Scholar 

  21. Feldman A, Aigner E, Weghuber D, Paulmichl K. The potential role of iron and copper in pediatric obesity and nonalcoholic fatty liver disease. Biomed Res Int. 2015;2015:7.

    Article  Google Scholar 

  22. Ullah A, Ud Din A, Ding W, Shi Z, Pervaz S, Shen B. A narrative review: CXC chemokines influence immune surveillance in obesity and obesity-related diseases: type 2 diabetes and nonalcoholic fatty liver disease. Rev Endocr Metab Disord. 2023;4:611–31.

    Article  Google Scholar 

  23. Moghbeli M, Khedmatgozar H, Yadegari M, Avan A, Ferns GA, Ghayour Mobarhan M. Cytokines and the immune response in obesity-related disorders. Adv Clin Chem. 1st ed. 2021. p. 135–68.

  24. Peña A, Olson ML, Ayers SL, Sears DD, Vega-López S, Colburn AT, et al. Inflammatory mediators and type 2 diabetes risk factors before and in response to Lifestyle intervention among latino adolescents with obesity. Nutrients. 2023;15:2442.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Stoppa-Vaucher S, Dirlewanger MA, Meier CA, De Moerloose P, Reber G, Roux-Lombard P, et al. Inflammatory and prothrombotic states in obese children of European descent. Obesity. 2012;20:1662–8.

    Article  CAS  PubMed  Google Scholar 

  26. Ruotsalainen E, Salmenniemi U, Vauhkonen I, Pihlajam̈aki J, Punnonen K, Kainulainen S, et al. Changes in inflammatory cytokines are related to impaired glucose tolerance in offspring of type 2 diabetic subjects. Diabetes Care. 2006;29:2714–20.

    Article  CAS  PubMed  Google Scholar 

  27. Aygun AD, Gungor S, Ustundag B, Gurgoze MK, Sen Y. Proinflammatory cytokines and leptin are increased in serum of prepubertal obese children. Mediators Inflamm. 2005;2005:180–3.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Rohm TV, Meier DT, Olefsky JM, Donath MY. Inflammation in obesity, diabetes, and related disorders. Immunity. 2022;55:31–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nicol LE, Grant WF, Comstock SM, Nguyen ML, Smith MS, Grove KL, et al. Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates. J Endocrinol. 2013;217:207–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Almheiri A, Alhammadi A, AlShehhi, Fatima Mohammad A, Alshamsi R, Alzaman K, Jabeen S, et al. Biomarkers for Prediabetes, type 2 diabetes, and Associated complications. Am J Heal Med Nurs Pract. 2023;9:pp1–21.

    Article  Google Scholar 

  31. Flisiak-Jackiewicz M, Bobrus-Chociej A, Tarasów E, Wojtkowska M, Białokoz-Kalinowska I, Lebensztejn DM. Predictive Role of Interleukin-18 in Liver Steatosis in Obese Children. Can J Gastroenterol Hepatol. 2018;2018.

  32. Dong G, Liang L, Fu J, Zou C. Serum interleukin-18 levels are raised in diabetic ketoacidosis in Chinese children with type 1 diabetes mellitus. Indian Pediatr. 2007;44:732–6.

    PubMed  Google Scholar 

  33. Svensson J, Eising S, Hougaard DM, Mortensen HB, Skogstrand K, Simonsen LB, et al. Few differences in cytokines between patients newly diagnosed with type 1 diabetes and their healthy siblings. Hum Immunol. 2012;73:1116–26.

    Article  CAS  PubMed  Google Scholar 

  34. Heier M, Margeirsdottir HD, Brunborg C, Hanssen KF, Dahl-Jørgensen K, Seljeflot I. Inflammation in childhood type 1 diabetes: influence of glycemic control. Atherosclerosis. 2015;238:33–7.

    Article  CAS  PubMed  Google Scholar 

  35. Harms RZ, Yarde DN, Guinn Z, Lorenzo-Arteaga KM, Corley KP, Cabrera MS, et al. Increased expression of IL-18 in the serum and islets of type 1 diabetics. Mol Immunol. 2015;64:306–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Jung C, Gerdes N, Fritzenwanger M, Figulla HR. Circulating levels of interleukin-1 family cytokines in overweight adolescents. Mediators Inflamm. 2010;2010:1–7.

    Article  Google Scholar 

  37. Khalil RG, Abdel-Moneim A, Yousef AI, Abdel-Rahman H, Zanaty MI, El-Sayed A. Association of interleukin-2, interleukin-21 and interleukin-23 with hyperlipidemia in pediatric type 1 diabetes. Mol Biol Rep. 2021;48:5421–33.

    Article  CAS  PubMed  Google Scholar 

  38. Iacomino G, Siani A. Role of microRNAs in obesity and obesity-related diseases. Genes Nutr. 2017;12:1223.

    Article  Google Scholar 

  39. Mohany KM, Rugaie O, Al, Al-wutayd O, Al-nafeesah A. Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with/without type 2 diabetes: a case control study. BMC Endocr Disord. 2021;21:21.

    Article  Google Scholar 

  40. Reinehr T. Inflammatory markers in children and adolescents with type 2 diabetes mellitus. Clin Chim Acta. 2019. p. 100–7.

  41. Smitka K, Marešová D. Adipose tissue as an endocrine organ: an update on pro-inflammatory and anti-inflammatory microenvironment. Prague Med Rep. 2015;116:87–111.

    Article  PubMed  Google Scholar 

  42. Hagman E, Besor O, Hershkop K, Santoro N, Pierpont B, Mata M, et al. Relation of the degree of obesity in childhood to adipose tissue insulin resistance. Acta Diabetol. 2019;56:219–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Flores-Cortez YA, Barragán-Bonilla MI, Mendoza-Bello JM, González-Calixto C, Flores-Alfaro E, Espinoza-Rojo M. Interplay of retinol binding protein 4 with obesity and associated chronic alterations (review). Mol Med Rep. 2022;26:244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Balagopal P, Graham TE, Kahn BB, Altomare A, Funanage V, George D. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: Association with subclinical inflammation. J Clin Endocrinol Metab. 2007;92:1971–4.

    Article  CAS  PubMed  Google Scholar 

  45. Camilli C, Hoeh AE, De Rossi G, Moss SE, Greenwood J. LRG1: an emerging player in disease pathogenesis. J Biomed Sci. 2022;29:1–29.

    Article  Google Scholar 

  46. Alhammad R, Abu-Farha M, Hammad MM, Thanaraj TA, Channanath A, Alam-Eldin N, et al. Increased LRG1 levels in overweight and obese adolescents and its association with Obesity Markers, including leptin, Chemerin, and high sensitivity C-Reactive protein. Int J Mol Sci. 2022;23:1–11.

    Article  Google Scholar 

  47. El-Alameey IR, Fadl NN, Abdel Hameed ER, Sherif LS, Ahmed HH. Clinical relevance of transforming growth factor-β1, interleukin-6 and haptoglobin for prediction of obesity complications in prepubertal Egyptian children. Maced J Med Sci. 2015;3:105–10.

    Article  Google Scholar 

  48. Serbis A, Giapros V, Challa A, Chaliasos N, Siomou E. Elevated 1-hour post-load plasma glucose identifies obese youth with abnormal glucose metabolism and an unfavourable inflammatory profile. Clin Endocrinol (Oxf). 2018;89:757–64.

    Article  CAS  PubMed  Google Scholar 

  49. Lopez-Sandoval J, Sanchez-Enriquez S, Rivera-Leon EA, Bastidas-Ramirez BE, Garcia-Garcia MR, Gonzalez-Hita ME. Cardiovascular risk factors in adolescents: role of insulin resistance and obesity. Acta Endocrinol (Copenh). 2018;14:330–7.

    CAS  Google Scholar 

  50. Oluwagbemigun K, Buyken AE, Alexy U, Schmid M, Herder C, Nöthlings U. Developmental trajectories of body mass index from childhood into late adolescence and subsequent late adolescence-young adulthood cardiometabolic risk markers. Cardiovasc Diabetol. 2019;18:1–14.

    Article  Google Scholar 

  51. Snell-Bergeon JK, West NA, Mayer-Davis EJ, Liese AD, Marcovina SM, D’Agostino RB, et al. Inflammatory markers are increased in youth with type 1 diabetes: the SEARCH case-control study. J Clin Endocrinol Metab. 2010;95:2868–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. G B, U M. Selected cytokines (Il-6, Il-8, Il-10, MCP-1, TNF-alpha) in children and adolescents with atherosclerosis risk factors: obesity, hypertension, diabetes. Wiad Lek (Warsaw Pol 1960). 2003;56:109–16.

    Google Scholar 

  53. Nascimento H, Vieira E, Coimbra S, Catarino C, Costa E, Bronze-Da-Rocha E, et al. Adipokine gene single-nucleotide polymorphisms in Portuguese obese adolescents: associations with plasma concentrations of adiponectin, resistin, IL-6, IL-1β, and TNF-α. Child Obes. 2016;12:300–13.

    Article  PubMed  Google Scholar 

  54. Tam CS, Garnett SP, Cowell CT, Heilbronn LK, Lee JW, Wong M, et al. IL-6, IL-8 and IL-10 levels in healthy weight and overweight children. Horm Res Paediatr. 2010;73:128–34.

    Article  CAS  PubMed  Google Scholar 

  55. Utsal L, Tillmann V, Zilmer M, Mäestu J, Purge P, Jürimäe J, et al. Elevated serum IL-6, IL-8, MCP-1, CRP, and IFN-γ levels in 10- to 11-year-old boys with increased BMI. Horm Res Paediatr. 2012;78:31–9.

    Article  CAS  PubMed  Google Scholar 

  56. Moschen HTAR. Christian. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med. 2008;103:398–406.

    Google Scholar 

  57. Zhang C. The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol. 2008;103:398–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Erbaǧci AB, Tarakçioǧlu M, Coşkun Y, Sivasli E, Sibel Namiduru E. Mediators of inflammation in children with type I diabetes mellitus: cytokines in type I diabetic children. Clin Biochem. 2001;34:645–50.

    Article  PubMed  Google Scholar 

  59. Roth CL, Kratz M, Ralston MM, Reinehr T. Changes in adipose-derived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children. Metabolism. 2011;60:445–52.

    Article  CAS  PubMed  Google Scholar 

  60. Herder C, Baumert J, Thorand B, Martin S, Löwel H, Kolb H, et al. Chemokines and incident coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Arterioscler Thromb Vasc Biol. 2006;26:2147–52.

    Article  CAS  PubMed  Google Scholar 

  61. Zeyda M, Farmer D, Todoric J, Aszmann O, Speiser M, Györi G, et al. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes. 2007;31:1420–8.

    Article  CAS  Google Scholar 

  62. Zeyda M, Stulnig TM. Adipose tissue macrophages. Immunol Lett. 2007;112:61–7.

    Article  CAS  PubMed  Google Scholar 

  63. Bhatt SP, Guleria R, Kabra SK. Metabolic alterations and systemic inflammation in overweight/obese children with obstructive sleep apnea. PLoS ONE. 2021;16:1–14.

    Article  Google Scholar 

  64. Lima RS, Mattos RT, Medeiros NI, Kattah FM, Julya R, Nascimento S, et al. CXCL8 expression and methylation are correlated with anthropometric and metabolic parameters in childhood obesity. Cytokine. 2021;143:155538.

    Article  CAS  PubMed  Google Scholar 

  65. Abdelhamid ER, Kamhawy AH, Ahmed HH, Abu Shady MM, Eladawy R, Megawer AS, et al. Role of inflammatory cytokines in obese and nonobese Diabetic Children. Maced J Med Sci. 2020;8:858–65.

    Article  Google Scholar 

  66. Kupca S, Jurka A, Marksa I, Rinkuza I, Sipols AJ, Rumba-Rozenfelde I. Inflammatory cytokine IFNγ, IL-6, and IL-10 association with childhood obesity. Proc Latv Acad Sci Sect B Nat Exact Appl Sci. 2021;75:387–91.

    CAS  Google Scholar 

  67. ES AA, D FEA, H DA, M DS, AA MGED, E NA, et al. Utility of Adipokines and IL-10 in Association with Anthropometry in prediction of insulin resistance in obese children. Diabetes Metab Syndr Obes. 2022;15:3231–41.

    Article  Google Scholar 

  68. Lauridsen JK, Olesen RH, Vendelbo J, Hyde TM, Kleinman JE, Bibby BM, et al. High BMI levels associate with reduced mRNA expression of IL10 and increased mRNA expression of iNOS (NOS2) in human frontal cortex. Transl Psychiatry. 2017;7:e1044–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yao CJ, Du W, Chen HB, Xiao S, Wang CH, Fan ZL. Associations of IL-10 gene polymorphisms with acute myeloid leukemia in Hunan, China. Asian Pac J Cancer Prev. 2013;14:2439–42.

    Article  PubMed  Google Scholar 

  70. Kulshrestha H, Gupta V, Mishra S, Mahdi AA, Awasthi S, Kumar S. Interleukin-10 as a novel biomarker of metabolic risk factors. Diabetes Metab Syndr Clin Res Rev. 2018;12:543–7.

    Article  Google Scholar 

  71. Chang JS, Bai CH, Huang ZC, Owaga E, Chao KC, Chang CC, et al. Interleukin 10 and clustering of metabolic syndrome components in pediatrics. Eur J Clin Invest. 2014;44:384–94.

    Article  CAS  PubMed  Google Scholar 

  72. Liu Y, Xu D, Yin C, Wang S, Wang M, Xiao Y. IL-10/STAT3 is reduced in childhood obesity with hypertriglyceridemia and is related to triglyceride level in diet-induced obese rats. BMC Endocr Disord. 2018;18:1–9.

    Article  Google Scholar 

  73. Toubal A, Kiaf B, Beaudoin L, Cagninacci L, Rhimi M, Fruchet B et al. Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity. Nat Commun. 2020;11.

  74. Carolan E, Tobin LM, Mangan BA, Corrigan M, Gaoatswe G, Byrne G, et al. Altered distribution and increased IL-17 production by Mucosal-Associated Invariant T Cells in adult and childhood obesity. J Immunol. 2015;194:5775–80.

    Article  CAS  PubMed  Google Scholar 

  75. Bergin R, Kinlen D, Kedia-Mehta N, Hayes E, Cassidy FC, Cody D, et al. Mucosal-associated invariant T cells are associated with insulin resistance in childhood obesity, and disrupt insulin signalling via IL-17. Diabetologia. 2022;65:1012–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Guo S, Mao X, Liu J. Multi-faceted roles of C1q/TNF-related proteins family in atherosclerosis. Front Immunol. 2023;14:1253433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Arking A, Sarver DC, Magge SN, Wong GW, Wolf RM. Novel adipokines CTRP1, CTRP9, and FGF21 in Pediatric Type 1 and type 2 diabetes: a cross-sectional analysis. Horm Res Paediatr. 2022;95:43–50.

    Article  CAS  PubMed  Google Scholar 

  78. Wolf RM, Jaffe AE, Rodriguez S, Lei X, Sarver DC, Straub AT, et al. Altered adipokines in obese adolescents: a cross-sectional and longitudinal analysis across the spectrum of glycemia. Am J Physiol - Endocrinol Metab. 2021;320:E1044–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Erbaş İM, Paketçi A, Turan S, Şişman AR, Demir K, Böber E, et al. Low complement C1q/TNF-related Protein-13 levels are Associated with childhood obesity but not binge eating disorder. J Clin Res Pediatr Endocrinol. 2022;14:179–87.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Shanaki M, Fadaei R, Moradi N, Emamgholipour S, Poustchi H. The circulating CTRP13 in type 2 diabetes and non-alcoholic. Fat Liver Patients. 2016;1–11.

  81. Rosa JS, Mitsuhashi M, Oliver SR, Ogura M, Flores RL, Pontello AM, et al. Ex vivo TCR-induced leukocyte gene expression of inflammatory mediators is increased in type 1 diabetic patients but not in overweight children. Diabetes Metab Res Rev. 2014;32:13–23.

    Google Scholar 

  82. Redondo M, Rodriguez L, Haymond M, Hampe C, Smith E, Balasubramanyam A, et al. Serum adiposity-induced biomarkers in obese and lean children with recently diagnosed autoimmune type 1 diabetes. Pediatr Diabetes. 2014;15:543–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Pawelczak M, Rosenthal J, Milla S, Liu YH, Shah B. Evaluation of the pro-inflammatory cytokine tumor necrosis Factor-α in adolescents with polycystic ovary syndrome. J Pediatr Adolesc Gynecol. 2014;27:356–9.

    Article  PubMed  PubMed Central  Google Scholar 

  84. El-Ayash H, Puyau M, Bacha F, Hyperglycemia. A determinant of cardiac autonomic dysfunction in youth with obesity across the spectrum of glycemic regulation. Pediatr Obes. 2023;18:1–8.

    Article  Google Scholar 

  85. Achenbach P, Hippich M, Zapardiel-Gonzalo J, Karges B, Holl RW, Petrera A, et al. A classification and regression tree analysis identifies subgroups of childhood type 1 diabetes. eBioMedicine. 2022;82:104118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wankhade UD, Lee JH, Dagur PK, Yadav H, Shen M, Chen W, et al. TGF-β receptor 1 regulates progenitors that promote browning of white fat. Mol Metab. 2018;16:160–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lee MJ. Transforming growth factor beta superfamily regulation of adipose tissue biology in obesity. Biochim Biophys Acta - Mol Basis Dis. 2018;1864:1160–71.

    Article  CAS  PubMed  Google Scholar 

  88. Noori S, Mirzababaei A, Shiraseb F, Bagheri R, Clark CCT, Wong A et al. The Association of Inflammatory Markers, IL-1 α and TGF- β, with Dietary Insulin Load and Dietary Insulin Index in Overweight and Obese Women with Healthy and Unhealthy Metabolic Phenotypes: A Cross-Sectional Study. Int J Clin Pract. 2022;2022.

  89. Kinik ST, Özbek N, Yuce M, Yazici AC, Verdi H, Ataç FB. PAI-1 gene 4G/5G polymorphism, cytokine levels and their relations with metabolic parameters in obese children. Thromb Haemost. 2008;99:352–6.

    Article  CAS  PubMed  Google Scholar 

  90. Kanra AR, Tulgar-Kinik S, Verdi H, Belgin Ataç F, Yazici AC, Özbek N. Transforming growth factor-beta1 (509 C/T, 915 G/C, 869 T/C) polymorphisms are not related to obesity in Turkish children. Turk J Pediatr. 2011;53:645–50.

    PubMed  Google Scholar 

  91. Fain JN, Tichansky DS, Madan AK. Transforming growth factor β1 release by human adipose tissue is enhanced in obesity. Metabolism. 2005;54:1546–51.

    Article  CAS  PubMed  Google Scholar 

  92. Mattos RT, Medeiros NI, Menezes CA, Fares RCG, Franco EP, Dutra WO, et al. Chronic low-grade inflammation in childhood obesity is associated with decreased il-10 expression by monocyte subsets. PLoS ONE. 2016;11:1–14.

    Article  Google Scholar 

  93. Makowski LM, Leffers M, Waltenberger J, Pardali E. Transforming growth factor-β1 signalling triggers vascular endothelial growth factor resistance and monocyte dysfunction in type 2 diabetes mellitus. J Cell Mol Med. 2021;25:5316–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Correia-Costa L, Morato M, Sousa T, Cosme D, Guimarães JT, Guerra A, et al. Urinary fibrogenic cytokines ET-1 and TGF-β1 are associated with urinary angiotensinogen levels in obese children. Pediatr Nephrol. 2016;31:455–64.

    Article  PubMed  Google Scholar 

  95. Mirea AM, Tack CJ, Chavakis T, Joosten LAB, Toonen EJM. IL-1 family cytokine pathways underlying NAFLD: towards New Treatment Strategies. Trends Mol Med. 2018;24:458–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Pihlajamäki J, Kuulasmaa T, Kaminska D, Simonen M, Kärjä V, Grönlund S, et al. Serum interleukin 1 receptor antagonist as an independent marker of non-alcoholic steatohepatitis in humans. J Hepatol. 2012;56:663–70.

    Article  PubMed  Google Scholar 

  97. Lischka J, Schanzer A, Hojreh A, Ba-Ssalamah A, de Gier C, Valent I, et al. Circulating microRNAs 34a, 122, and 192 are linked to obesity-associated inflammation and metabolic disease in pediatric patients. Int J Obes. 2021;45:1763–72.

    Article  CAS  Google Scholar 

  98. Perito ER, Ajmera V, Bass NM, Rosenthal P, Lavine JE, Schwimmer JB, et al. Association between cytokines and liver histology in children with nonalcoholic fatty liver disease. Hepatol Commun. 2017;1:609–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Fain JN. Release of inflammatory mediators by human adipose tissue is enhanced in obesity and primarily by the nonfat cells: A review. Mediators Inflamm. 2010;2010.

  100. Tragomalou A, Paltoglou G, Manou M, Kostopoulos IV, Loukopoulou S, Binou M, et al. Non-traditional Cardiovascular risk factors in adolescents with obesity and metabolic syndrome May Predict Future Cardiovascular Disease. Nutrients. 2023;15:4342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Mandato C, Lucariello S, Licenziati MR, Franzese A, Spagnuolo MI, Ficarella R, et al. Metabolic, hormonal, oxidative, and inflammatory factors in pediatric obesity-related liver disease. J Pediatr. 2005;147:62–6.

    Article  CAS  PubMed  Google Scholar 

  102. de Assunção SNF, Sorte NCAB, Alves CDAD, Mendes PSA, Alves CRB, Silva LR. Inflammatory cytokines and non-alcoholic fatty liver disease (NAFLD) in obese children and adolescents. Nutr Hosp. 2018;35:78–83.

    PubMed  Google Scholar 

  103. Das SK, Balakrishnan V. Role of cytokines in the pathogenesis of non-alcoholic fatty liver disease. Indian J Clin Biochem. 2011;26:202–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Crudele A, Dato S, Re O, Lo, Maugeri A, Sanna P, Giallongo S, et al. Pediatric non-alcoholic fatty liver disease is affected by Genetic Variants Involved in Lifespan/Healthspan. J Pediatr Gastroenterol Nutr. 2021;73:161–8.

    Article  CAS  PubMed  Google Scholar 

  105. El Amrousy D, El-Afify D. Osteocalcin and osteoprotegerin levels and their relationship with adipokines and proinflammatory cytokines in children with nonalcoholic fatty liver disease. Cytokine. 2020;135:155215.

    Article  PubMed  Google Scholar 

  106. Zolfaghari H, Askari G, Siassi F, Feizi A, Sotoudeh G. Intake of nutrients, fiber, and sugar in patients with nonalcoholic fatty liver disease in comparison to healthy individuals. Int J Prev Med. 2016;2016August.

  107. Skaaby T, Husemoen LLN, Borglykke A, Jørgensen T, Thuesen BH, Pisinger C, et al. Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine. 2014;47:213–20.

    Article  CAS  PubMed  Google Scholar 

  108. Roth CL, Elfers CT, Figlewicz DP, Melhorn SJ, Morton GJ, Hoofnagle A, et al. Vitamin D deficiency in obese rats exacerbates nonalcoholic fatty liver disease and increases hepatic resistin and toll-like receptor activation. Hepatology. 2012;55:1103–11.

    Article  CAS  PubMed  Google Scholar 

  109. Loureiro C, Martínez-Aguayo A, Campino C, Carvajal C, Fardella C, García H. Hepatic steatosis as diabetes type 2 predictor. Nutr Hosp. 2014;29:350–8.

    PubMed  Google Scholar 

  110. 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;10:1329.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Ceccarelli S, Panera N, Mina M, Gnani D, Crudele CDSA, Rychlicki C, et al. LPS-induced TNF-alpha factor mediates pro-inflammatory and pro-fibrogenic pattern in non-alcoholic fatty liver disease. Oncotarget. 2015;6:34–52.

    Article  Google Scholar 

  112. Hernández MJG, Klünder M, Nieto NG, Alvarenga JCL, Gil JV, Huerta SF, et al. Pediatric Visceral Adiposity Index Adaptation correlates with Homa-IR, Matsuda, and transaminases. Endocr Pract. 2018;24:294–301.

    Article  PubMed  Google Scholar 

  113. Jonas W, Schürmann A. Genetic and epigenetic factors determining NAFLD risk. Mol Metab. 2021;50:101111.

    Article  CAS  PubMed  Google Scholar 

  114. Dongiovanni P, Crudele A, Panera N, Romito I, Meroni M, De Stefanis C, et al. β-Klotho gene variation is associated with liver damage in children with NAFLD. J Hepatol. 2020;72:411–9.

    Article  CAS  PubMed  Google Scholar 

  115. Cabrera D, Cabello-Verrugio C, Solís N, Martín DS, Cofré C, Pizarro M, et al. Somatotropic axis dysfunction in non-alcoholic fatty liver disease: beneficial hepatic and systemic effects of hormone supplementation. Int J Mol Sci. 2018;19:1339.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Mosca A, Della Volpe L, Alisi A, Panera N, Maggiore G, Vania A. The role of the GH/IGF1 Axis on the development of MAFLD in Pediatric patients with obesity. Metabolites. 2022;12:1221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kim JS, Lê KA, Mahurkar S, Davis JN, Goran MI. Influence of elevated liver fat on circulating adipocytokines and insulin resistance in obese hispanic adolescents. Pediatr Obes. 2012;7:158–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Shi JQ, Shen WX, Wang XZ, Huang K, Zou CC. Relationship between immune parameters and non-alcoholic fatty liver disease in obese children. Indian Pediatr. 2017;54:825–9.

    Article  PubMed  Google Scholar 

  119. Abdallah A, El Mashad G. Interleukin 10, thyroid status and ferritin are non-invasive prognostic biomarkers for diagnosis of fatty liver disease in children. J Int Res Med. 2015;8:85–93.

    Google Scholar 

  120. Kim HM, Lee BR, Lee ES, Kwon MH, Huh JH, Kwon BE, et al. INKT cells prevent obesity-induced hepatic steatosis in mice in a C-C chemokine receptor 7-dependent manner. Int J Obes. 2018;42:270–9.

    Article  CAS  Google Scholar 

  121. Mosca A, Crudele A, Smeriglio A, Braghini MR, Panera N, Comparcola D, et al. Antioxidant activity of Hydroxytyrosol and vitamin E reduces systemic inflammation in children with paediatric NAFLD. Dig Liver Dis. 2021;53:1154–8.

    Article  CAS  PubMed  Google Scholar 

  122. Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell. 2021;184:2537–64.

    Article  CAS  PubMed  Google Scholar 

  123. Zhang C, Yang M, Ericsson AC. The potential gut microbiota-mediated treatment options for Liver Cancer. Front Oncol. 2020;10:1–8.

    Google Scholar 

  124. Cairoli V, De Matteo E, Rios D, Lezama C, Galoppo M, Casciato P, et al. Hepatic lymphocytes involved in the pathogenesis of pediatric and adult non-alcoholic fatty liver disease. Sci Rep. 2021;11:1–10.

    Article  Google Scholar 

  125. Akbulut UE, Emeksiz HC, Citli S, Cebi AH, Korkmaz HAA, Baki G. IL-17A, MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease. J Pediatr (Rio J). 2019;95:350–7.

    Article  PubMed  Google Scholar 

  126. Barretto JR, Boa-Sorte N, Vinhaes CL, Malta-Santos H, Rebouças-Silva J, Ramos CF, et al. Heightened plasma levels of transforming growth factor beta (TGF-β) and increased degree of systemic biochemical perturbation characterizes hepatic steatosis in overweight pediatric patients: a cross-sectional study. Nutrients. 2020;12:1650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Galuppo B, Agazzi C, Pierpont B, Chick J, Li Z, Caprio S, et al. Growth differentiation factor 15 (GDF15) is associated with non-alcoholic fatty liver disease (NAFLD) in youth with overweight or obesity. Nutr Diabetes. 2022;12:15–8.

    Article  Google Scholar 

  128. Ibrahim SH, Hirsova P, Gores GJ. Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation. Gut. 2018;67:963–72.

    Article  CAS  PubMed  Google Scholar 

  129. Alisi A, Nobili V, Ceccarelli S, Panera N, De Stefanis C, De Vito R, et al. Plasma high mobility group box 1 protein reflects fibrosis in pediatric nonalcoholic fatty liver disease. Expert Rev Mol Diagn. 2014;14:763–71.

    Article  CAS  PubMed  Google Scholar 

  130. Mittal M, Jain V. Management of obesity and its complications in children and adolescents. Indian J Pediatr. 2021;88:1222–34.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Della L, Codella R. Cytokine and growth factor reviews Exercise tolls the bell for key mediators of low-grade inflammation in dysmetabolic conditions. Cytokine Growth Factor Rev. 2021;62:83–93.

    Article  Google Scholar 

  132. Rosa JS, Heydari S, Oliver SR, Flores RL, Pontello AM, Ibardolaza M, et al. Inflammatory cytokine profiles during exercise in obese, diabetic, and healthy children. JCRPE J Clin Res Pediatr Endocrinol. 2011;3:115–21.

    Article  PubMed  Google Scholar 

  133. Rosa JS, Oliver SR, Flores RL, Ngo J, Milne GL, Zaldivar FP, et al. Altered inflammatory, oxidative, and metabolic responses to exercise in pediatric obesity and type 1 diabetes. Pediatr Diabetes. 2011;12:464–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kim JS, Lee YH, Kim JC, Ko YH, Yoon CS, Yi HK. Effect of exercise training of different intensities on anti-inflammatory reaction in streptozotocin-induced diabetic rats. Biol Sport. 2014;31:73–9.

    Article  CAS  PubMed  Google Scholar 

  135. Simpson RJ, Kunz H, Agha N, Graff R. Exercise and the regulation of Immune functions. Mol Cell Regul Adapt Exerc. 2015.

  136. Nash D, Hughes MG, Butcher L, Aicheler R, Smith P, Cullen T, et al. IL-6 signaling in acute exercise and chronic training: potential consequences for health and athletic performance. Scand J Med Sci Sport. 2022;33:4–19.

    Article  Google Scholar 

  137. Steensberg A, Fischer CP, Keller C, Møller K, Pedersen BK. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol - Endocrinol Metab. 2003;285:433–7.

    Article  Google Scholar 

  138. Aminianfar FAMFA, Shirzad KDN, Larijani CCTCB. The effect of Mediterranean diet on inflammatory biomarkers and components of metabolic syndrome in adolescent girls. J Endocrinol Invest. 2023;46:1995–2004.

    Article  PubMed  Google Scholar 

  139. Valle-Martos R, Jiménez-Reina L, Cañete R, Martos R, Valle M, Cañete MD. Changes in liver enzymes are associated with changes in insulin resistance, inflammatory biomarkers and leptin in prepubertal children with obesity. Ital J Pediatr. 2023;49:1–10.

    Article  Google Scholar 

  140. Ye C, Brand D, Zheng SG, Targeting. IL-2: an unexpected effect in treating immunological diseases. Signal Transduct Target Ther. 2018;3:2.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Rosenzwajg M, Salet R, Lorenzon R, Tchitchek N, Roux A, Bernard C, et al. Low-dose IL-2 in children with recently diagnosed type 1 diabetes: a phase I/II randomised, double-blind, placebo-controlled, dose-finding study. Diabetologia. 2020;63:1808–21.

    Article  CAS  PubMed  Google Scholar 

  142. Peterson LB, Bell CJM, Howlett SK, Pekalski ML, Brady K, Hinton H, et al. A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease. J Autoimmun. 2018;95:1–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Reinehr T, Karges B, Meissner T, Wiegand S, Stoffel-Wagner B, Holl RW, et al. Inflammatory markers in obese adolescents with type 2 diabetes and their relationship to hepatokines and adipokines. J Pediatr. 2016;173:131–5.

    Article  CAS  PubMed  Google Scholar 

  144. Fordjour L, Cai C, Bronshtein V, Bronshtein M, Aranda JV, Beharry KD. Growth factors in the fetus and pre-adolescent offspring of hyperglycemic rats. Diabetes Vasc Dis Res. 2021;18.

  145. Mizgier M, Jarząbek-Bielecka G, Wendland N, Jodłowska-Siewert E, Nowicki M, Brożek A, et al. Relation between inflammation, oxidative stress, and macronutrient intakes in normal and excessive body weight adolescent girls with clinical features of polycystic ovary syndrome. Nutrients. 2021;13:896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Khashchenko E, Vysokikh M, Uvarova E, Krechetova L, Vtorushina V, Ivanets T, et al. Activation of systemic inflammation and oxidative stress in adolescent girls with polycystic ovary syndrome in combination with metabolic disorders and excessive body weight. J Clin Med. 2020;9:1399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Paltoglou G, Schoina M, Valsamakis G, Salakos N, Avloniti A, Chatzinikolaou A, et al. Interrelations among the adipocytokines leptin and adiponectin, oxidative stress and aseptic inflammation markers in pre- and early-pubertal normal-weight and obese boys. Endocrine. 2017;55:925–33.

    Article  CAS  PubMed  Google Scholar 

  148. Shokri E, Heidarianpour A, Razavi Z. Positive effect of combined exercise on adipokines levels and pubertal signs in overweight and obese girls with central precocious puberty. Lipids Health Dis. 2021;20:152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Jiang Y, Yang L, Chen H, Chen J, Yang L, Wang Z, et al. Network pharmacology combined with lipidomics to reveal the regulatory effects and mechanisms of Kangzao granules in the hypothalamus of rats with central precocious puberty. J Pharm Biomed Anal. 2024;242:116059.

    Article  CAS  PubMed  Google Scholar 

  150. Lischka J, Schanzer A, de Gier C, Greber-Platzer S, Zeyda M. Macrophage-associated markers of metaflammation are linked to metabolic dysfunction in pediatric obesity. Cytokine. 2023;171:156372.

    Article  CAS  PubMed  Google Scholar 

  151. Yuan X, Chen R, McCormick KL, Zhang Y, Lin X, Yang X. The role of the gut microbiota on the metabolic status of obese children. Microb Cell Fact. 2021;20:20.

    Article  Google Scholar 

  152. Sanches MD, Goldberg TBL, Rizzo A, da CB VN, Mosca LN, Romagnoli GG, et al. Inflammatory cytokines and chemokines in obese adolescents with antibody against to adenovirus 36. Sci Rep. 2023;13:9918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Bugajska J, Berska J, Wójcik M, Sztefko K. Amino acid profile in overweight and obese prepubertal children– can simple biochemical tests help in the early prevention of associated comorbidities? Front Endocrinol (Lausanne). 2023;14:1274011.

    Article  PubMed  Google Scholar 

  154. Visuthranukul C, Kwanbunbumpen T, Chongpison Y, Chamni S, Panichsillaphakit E, Uaariyapanichkul J, et al. The impact of Dietary Fiber as a prebiotic on inflammation in children with obesity. Foods. 2022;11:2856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Taghizadeh N, Mohammadi S, Yousefi Z, Golpour P, Taheri A, Maleki MH, et al. Assessment of global histone acetylation in pediatric and adolescent obesity: correlations with SIRT1 expression and metabolic-inflammatory profiles. PLoS ONE. 2023;18:e0293217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Thürmann L, Bauer M, Ferland M, Messingschlager M, Schikowski T, Von Berg A, et al. Undiagnosed Pediatric elevated blood pressure is characterized by induction of Proinflammatory and Cytotoxic mediators. Hypertension. 2023;80:2425–36.

    Article  PubMed  Google Scholar 

  157. Yang Y, Li J, Zhou Z, Wu S, Zhao J, Jia W, et al. Gut microbiota perturbation in early life could Influence Pediatric blood pressure regulation in a sex-dependent manner in juvenile rats. Nutrients. 2023;15:2661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Prunicki M, Cauwenberghs N, Ataam JA, Movassagh H, Kim JB, Kuznetsova T, et al. Immune biomarkers link air pollution exposure to blood pressure in adolescents. Environ Heal Glob Access Sci Source. 2020;19:1–17.

    Google Scholar 

  159. Stinson SE, Jonsson AE, Andersen MK, Lund MAV, Holm LA, Fonvig CE, et al. High plasma levels of Soluble Lectin-like oxidized low-density lipoprotein Receptor-1 are Associated with inflammation and cardiometabolic risk profiles in Pediatric overweight and obesity. J Am Heart Assoc. 2023;12:e8145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Maggio ABR, Farpour-Lambert NJ, Aggoun Y, Galan K, Montecucco F, Mach F, et al. Serum cardiovascular risk biomarkers in pre-pubertal obese children. Eur J Clin Invest. 2018;48:e12995.

    Article  PubMed  Google Scholar 

  161. Thorsteinsdottir H, Salvador CL, Mjøen G, Lie A, Sugulle M, Tøndel C, et al. Growth differentiation factor 15 in children with chronic kidney Disease and after renal transplantation. Dis Markers. 2020;2020:8.

    Article  Google Scholar 

  162. Kamianowska M, Kamianowska A, Wasilewska A. Urinary levels of kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) in children and adolescents with hyperuricemia. Adv Med Sci. 2023;68:79–85.

    Article  CAS  PubMed  Google Scholar 

  163. 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 

Download references

Acknowledgements

West China Hospital and Sichuan University financially supported this study. BioRender.com was used to create the figures.

Funding

This work was supported by the National Natural Science Foundation of China (32070671, 32270690), the COVID-19 research projects of West China Hospital Sichuan University (Grant no. HX-2019-nCoV-057), and the regional innovation cooperation between Sichuan and Guangxi Provinces (2020YFQ0019).

Author information

Authors and Affiliations

  1. Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China

    Amin Ullah, Rajeev K. Singla, Zahra Batool, Dan Cao & Bairong Shen

  2. School of Pharmaceutical Sciences, Lovely Professional University, 144411, Phagwara, Punjab, India

    Rajeev K. Singla

Authors
  1. Amin Ullah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajeev K. Singla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zahra Batool
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dan Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bairong Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the work’s conception, drafting, illustration, and final revision. Each author reviewed and approved the final manuscript.

Corresponding author

Correspondence to Bairong Shen.

Ethics declarations

Ethical approval and consent to participate

Not applicable.

Consent for publication

All the authors approved the final version of the manuscript.

Conflict of interest

The authors say they have no commercial or financial ties that could be seen as a conflict of interest in our study. Because of this, there were no conflicts of interest in the study.

Additional information

Publisher’s Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ullah, A., Singla, R.K., Batool, Z. et al. Pro- and anti-inflammatory cytokines are the game-changers in childhood obesity-associated metabolic disorders (diabetes and non-alcoholic fatty liver diseases). Rev Endocr Metab Disord (2024). https://doi.org/10.1007/s11154-024-09884-y

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11154-024-09884-y

Keywords

Search

Navigation