Fatty liver and adipokines: converging pathways linking insulin resistance to early atherosclerosis in obese children and adolescents

INTRODUCTION: 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-media 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. CONTENT: A structured narrative review following SANRA guidance was conducted. PubMed/MEDLINE was searched from January 2000 to March 2025 for studies enrolling children aged 2-18 years with obesity and reporting cIMT measured by B-mode ultrasonography alongside NAFLD or adipokine measures. Quality was assessed using the Newcastle-Ottawa Scale (NOS) and AMSTAR-2. Across ten included studies (NOS scores: 5-8/9), obese children with NAFLD demonstrated consistently higher cIMT than controls (pooled weighted mean difference: +0.06 mm; 95% CI: 0.04-0.08 mm). Biopsy-proven nonalcoholic steatohepatitis independently predicted greater cIMT than simple steatosis (r=0.41; p<0.01). Resistin showed the strongest adipokine-cIMT association (r=0.47; p<0.001), with direct (β=0.31) and indirect effects via HOMA-IR (β=0.18) and high-sensitivity C-reactive protein (β=0.12). HMW-adiponectin deficiency, rather than total adiponectin, defined the preatherosclerotic phenotype. Chemerin correlated with cIMT (r=0.44; p<0.01) and metabolic syndrome score (β=0.39; p<0.001). Weight-loss intervention reduced cIMT by 0.03 mm (p<0.05), accompanied by adipokine normalization. SUMMARY AND OUTLOOK: 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.