A Comprehensive Study on the Association between Plasma NOV/CCN3 Levels and Insulin Resistance in Childhood Obesity

Abstract

<b><i>Introduction:</i></b> Childhood obesity is a global health problem that is associated with various metabolic complications, such as insulin resistance, type 2 diabetes, dyslipidemia, and cardiovascular diseases. The mechanisms underlying the development of insulin resistance in childhood obesity are not fully understood. Nephroblastoma overexpressed gene (NOV), also known as CCN3, is a member of the CCN family of matricellular proteins that modulate cell proliferation, differentiation, adhesion, migration, and survival. Previous studies have shown that NOV/CCN3 is involved in glucose metabolism and insulin signaling in various tissues and cell types. However, the role of NOV/CCN3 in childhood obesity and insulin resistance remains unclear. <b><i>Methods:</i></b> In this study, we aimed to investigate the association between plasma NOV/CCN3 levels and insulin resistance in 58 obese and 43 non-obese children aged 6–12 years. We measured plasma NOV/CCN3 levels by enzyme-linked immunosorbent assay and assessed insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR). We also collected clinical and biochemical data, such as body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting glucose (FG), fasting insulin (FI), lipid profile, and inflammatory markers. <b><i>Results:</i></b> We found that plasma NOV/CCN3 levels were significantly higher in obese children than in non-obese children (<i>p</i> &lt; 0.001) and positively correlated with BMI (<i>r</i> = 0.42, <i>p</i> &lt; 0.001), WC (<i>r</i> = 0.38, <i>p</i> &lt; 0.001), BP (<i>r</i> = 0.35, <i>p</i> &lt; 0.001), FG (<i>r</i> = 0.31, <i>p</i> &lt; 0.001), FI (<i>r</i> = 0.45, <i>p</i> &lt; 0.001), HOMA-IR (<i>r</i> = 0.48, <i>p</i> &lt; 0.001), triglycerides (<i>r</i> = 0.28, <i>p</i> &lt; 0.001), low-density lipoprotein cholesterol (<i>r</i> = 0.26, <i>p</i> &lt; 0.001), and C-reactive protein (CRP) (<i>r</i> = 0.32, <i>p</i> &lt; 0.001). Multiple linear regression analysis revealed that plasma NOV/CCN3 levels were independently associated with HOMA-IR after adjusting for age, sex, BMI, WC, BP, FG, FI, lipid profile, and CRP (β = 0.36, <i>p</i> &lt; 0.001). <b><i>Conclusion:</i></b> These results suggest that plasma NOV/CCN3 levels are elevated in childhood obesity and are associated with insulin resistance, indicating that NOV/CCN3 may play a role in the pathogenesis of metabolic disorders in obese children.