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

Abstract

Abstract 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.