{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:46:15Z","timestamp":1791974775788,"version":"4.4.0"},"reference-count":31,"publisher":"Walter de Gruyter GmbH","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2026-0302_abs_001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Childhood obesity drives nonalcoholic fatty liver disease (NAFLD) and adipokine dysregulation, converging on insulin resistance (IR) to promote subclinical vascular injury measurable as increased carotid intima\u2013media thickness (cIMT). Pediatric-specific mechanistic integration of these pathways with early atherosclerosis remains incompletely characterized. This review synthesizes evidence on NAFLD severity and cIMT in obese youth, examines the roles of resistin, high-molecular-weight (HMW) adiponectin, chemerin, and inflammatory mediators in IR-driven vascular remodeling, and evaluates their diagnostic and therapeutic implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0302_abs_002\">\n                    <jats:title>Content<\/jats:title>\n                    <jats:p>A structured narrative review following SANRA guidance was conducted. PubMed\/MEDLINE was searched from January 2000 to March 2025 for studies enrolling children aged 2\u201318 years with obesity and reporting cIMT measured by B-mode ultrasonography alongside NAFLD or adipokine measures. Quality was assessed using the Newcastle\u2013Ottawa Scale (NOS) and AMSTAR-2. Across ten included studies (NOS scores: 5\u20138\/9), obese children with NAFLD demonstrated consistently higher cIMT than controls (pooled weighted mean difference: +0.06 mm; 95% CI: 0.04\u20130.08 mm). Biopsy-proven nonalcoholic steatohepatitis independently predicted greater cIMT than simple steatosis (r=0.41; p&lt;0.01). Resistin showed the strongest adipokine\u2013cIMT association (r=0.47; p&lt;0.001), with direct (\u03b2=0.31) and indirect effects via HOMA-IR (\u03b2=0.18) and high-sensitivity C-reactive protein (\u03b2=0.12). HMW-adiponectin deficiency, rather than total adiponectin, defined the preatherosclerotic phenotype. Chemerin correlated with cIMT (r=0.44; p&lt;0.01) and metabolic syndrome score (\u03b2=0.39; p&lt;0.001). Weight-loss intervention reduced cIMT by 0.03 mm (p&lt;0.05), accompanied by adipokine normalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0302_abs_003\">\n                    <jats:title>Summary and Outlook<\/jats:title>\n                    <jats:p>NAFLD and adipokine dysregulation constitute interdigitated, IR-centered pathways associated with early atherosclerosis in obese youth, detectable from age 7 and partially reversible with timely intervention. A tiered algorithm incorporating BMI, liver enzymes, HOMA-IR, cIMT, and adipokine profiling is proposed for clinical risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2026-0302","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:59:13Z","timestamp":1791971953000},"source":"Crossref","is-referenced-by-count":0,"title":["Fatty liver and adipokines: converging pathways linking insulin resistance to early atherosclerosis in obese children and adolescents"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9585-9461","authenticated-orcid":false,"given":"Ashraf T.","family":"Soliman","sequence":"first","affiliation":[{"name":"Department of Pediatrics , Hamad General Hospital , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noora","family":"AlHumaidi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Hamad General Hospital , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Elawwa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Hamad General Hospital , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawzia","family":"Alyafei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Hamad General Hospital , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Hamed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Hamad General Hospital , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayma","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Hamad General Hospital , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9614-6511","authenticated-orcid":false,"given":"Nada","family":"Alaaraj","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Hamad General Hospital , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"2026101409590970271_j_jpem-2026-0302_ref_001","doi-asserted-by":"crossref","unstructured":"Pacifico, L, Cantisani, V, Ricci, P, Osborn, JF, Schiavo, E, Anania, C, et al.. Nonalcoholic fatty liver disease and carotid atherosclerosis in children. Pediatr Res 2008;63:423\u20137. https:\/\/doi.org\/10.1203\/pdr.0b013e318165b8e7.","DOI":"10.1203\/PDR.0b013e318165b8e7"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_002","doi-asserted-by":"crossref","unstructured":"Skinner, AC, Ravanbakht, SN, Skelton, JA, Perrin, EM, Armstrong, SC. Prevalence of obesity and severe obesity in US children, 1999\u20132016. Pediatrics 2018;141:e20173459. https:\/\/doi.org\/10.1542\/peds.2017-3459.","DOI":"10.1542\/peds.2017-3459"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_003","doi-asserted-by":"crossref","unstructured":"GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25\u00a0years. N\u00a0Engl J Med 2017;377:13\u201327. https:\/\/doi.org\/10.1056\/nejmoa1614362.","DOI":"10.1056\/NEJMoa1614362"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_012","doi-asserted-by":"crossref","unstructured":"Wunsch, R, de Sousa, G, Toschke, AM, Reinehr, T. Intima-media thickness in obese children before and after weight loss. Pediatrics 2006;118:2334\u201340. https:\/\/doi.org\/10.1542\/peds.2006-0302.","DOI":"10.1542\/peds.2006-0302"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_004","doi-asserted-by":"crossref","unstructured":"Lau, DCW, Dhillon, B, Yan, H, Szmitko, PE, Verma, S. Adipokines: molecular links between obesity and atherosclerosis. Am J Physiol Heart Circ Physiol 2005;288:H2031\u201341. https:\/\/doi.org\/10.1152\/ajpheart.01058.2004.","DOI":"10.1152\/ajpheart.01058.2004"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_005","doi-asserted-by":"crossref","unstructured":"Banerjee, D, Mani, A. Obesity\u2019s systemic impact: exploring molecular and physiological links to diabetes, cardiovascular disease, and heart failure. Front Endocrinol 2025;16:1681766. https:\/\/doi.org\/10.3389\/fendo.2025.1681766.","DOI":"10.3389\/fendo.2025.1681766"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_006","doi-asserted-by":"crossref","unstructured":"Landecho, MF, Tuero, C, Valent\u00ed, V, Bilbao, I, de la Higuera, M, Fr\u00fchbeck, G. Relevance of leptin and other adipokines in obesity-associated cardiovascular risk. Nutrients 2019;11:2664. https:\/\/doi.org\/10.3390\/nu11112664.","DOI":"10.3390\/nu11112664"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_007","doi-asserted-by":"crossref","unstructured":"Mantovani, RM, Rocha, NP, Magalh\u00e3es, DM, Barbosa, IG, Teixeira, AL, Sim\u00f5es, e, et al.. Early changes in adipokines from overweight to obesity in children and adolescents. J\u00a0Pediatr 2016;92:624\u201330. https:\/\/doi.org\/10.1016\/j.jped.2016.02.015.","DOI":"10.1016\/j.jped.2016.02.015"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_008","doi-asserted-by":"crossref","unstructured":"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\u20139. https:\/\/doi.org\/10.1002\/hep.20842.","DOI":"10.1002\/hep.20842"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_009","doi-asserted-by":"crossref","unstructured":"Cali, AM, De Oliveira, AM, Kim, H, Chen, S, Reyes-Mugica, M, Escalera, S, et al.. Glucose dysregulation and hepatic steatosis in obese adolescents: is there a link? Hepatology 2009;49:1896\u2013903. https:\/\/doi.org\/10.1002\/hep.22858.","DOI":"10.1002\/hep.22858"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_010","doi-asserted-by":"crossref","unstructured":"Manco, M, Bedogni, G, Monti, L, Morino, G, Natali, G, Nobili, V. 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Int J Mol Sci 2021;22:2163. https:\/\/doi.org\/10.3390\/ijms22042163.","DOI":"10.3390\/ijms22042163"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_026","doi-asserted-by":"crossref","unstructured":"Zhou, JC, Rifas-Shiman, SL, Haines, J, Jones, K, Oken, E. Adolescent overeating and binge eating behavior in relation to subsequent cardiometabolic risk outcomes. J\u00a0Eat Disord 2022;10:140. https:\/\/doi.org\/10.1186\/s40337-022-00660-4.","DOI":"10.1186\/s40337-022-00660-4"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_027","doi-asserted-by":"crossref","unstructured":"Kavey, RE, Daniels, SR, Lauer, RM, Atkins, DL, Hayman, LL, Taubert, K. American Heart Association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. J\u00a0Pediatr 2003;142:368\u201372.","DOI":"10.1067\/mpd.2003.205"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_028","unstructured":"Mihuta, MS, Paul, C, Borlea, A, Roi, CM, Pescari, D, Stoian, DL. Childhood obesity: systemic complications, early atherosclerosis and the value of carotid intima-media thickness. In: Ultrasound\u00a0\u2013\u00a0the next step in clinical evaluation. London: IntechOpen; 2025."},{"key":"2026101409590970271_j_jpem-2026-0302_ref_029","doi-asserted-by":"crossref","unstructured":"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\u201330. https:\/\/doi.org\/10.1038\/s41575-019-0169-z.","DOI":"10.1038\/s41575-019-0169-z"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_030","doi-asserted-by":"crossref","unstructured":"Sosanya, ME, Temple, JL. Two sides of a coin: molecular, metabolic, and phenotypic convergence in pediatric undernutrition and obesity. Curr Obes Rep 2026;15:16. https:\/\/doi.org\/10.1007\/s13679-026-00689-5.","DOI":"10.1007\/s13679-026-00689-5"},{"key":"2026101409590970271_j_jpem-2026-0302_ref_031","doi-asserted-by":"crossref","unstructured":"Tarantino, G, Citro, V, Balsano, C, Capone, D. Age and interleukin-15 levels are independently associated with intima-media thickness in obesity-related NAFLD patients. 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