Adipose tissue dysfunction is a key mechanism that leads to adiposity-based chronic disease. This study aimed to investigate the reliability of the adiponectin/leptin ratio (AdipoQ/Lep) as an adipose tissue and metabolic function biomarker in adults with obesity, without diabetes. Data were collected from a clinical trial conducted in 28 adults with obesity (mean body mass index: 35.4 ± 3.7 kg/m²) (NCT02169778). With the use of a forward stepwise multiple linear regression model to explore the relationship between AdipoQ/Lep and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), it was observed that 48.6% of HOMA-IR variance was explained by triacylglycerols, AdipoQ/Lep, and waist-to-hip ratio (P < 0.001), AdipoQ/Lep being the strongest independent predictor (Beta = −0.449, P < 0.001). A lower AdipoQ/Lep was correlated with higher body mass index (R_s = −0.490, P < 0.001), body fat mass (R_s = −0.486, P < 0.001), waist-to-height ratio (R_s = −0.290, P = 0.037), and plasma resistin (R_s = −0.365, P = 0.009). These data highlight the central role of adipocyte dysfunction in the pathogenesis of insulin resistance and emphasize that AdipoQ/Lep may be a promising early marker of insulin resistance development in adults with obesity.

NEW & NOTEWORTHY Adiponectin/leptin ratio, triacylglycerols, and waist-to-hip ratio explained almost half of HOMA-IR variance in the context of obesity. This study provides evidence to support adipose tissue dysfunction as a central feature of the pathophysiology of obesity and insulin resistance. Early identification of individuals at higher risk of developing metabolic complications through adipose tissue dysfunction assessment and the staging of obesity and its transient phenotypes can contribute to improve therapeutic decision-making.