The adiponectin/leptin ratio as a biomarker of adiposopathy and visceral adipose tissue accumulation: sex-specific mechanisms

Adipose tissue (AT) dysfunction, or adiposopathy, can lead to increased visceral AT (VAT) and metabolic damage. The adiponectin/leptin (A/L) ratio has been proposed as a biomarker of AT functionality. However, its participation in VAT accumulation and the impact of sex on these associations have not been evaluated.
In an analytical cross-sectional study, 60 adults (29 men, 31 women, aged 30–70 years, BMI 19–35 kg/m²) without diabetes, cardiovascular, or metabolic diseases were analyzed. Anthropometric data, fasting serum samples, and subcutaneous AT (SAT) biopsies were obtained. Morpho-functional AT characteristics included A/L ratio, histological adipocyte size, macrophage content (CD 68+ cells), and adipose insulin resistance (ADIPO-IR= fasting insulin (µU/mL) *glycerol (mmol/L)). Using multivariate and causal mediation models, we evaluated the associations of SAT characteristics with systemic IR (TyG index=TyG= ln [(triglycerides [mg/dL]*glucose [mg/dL])/2]), systemic inflammation (C-reactive protein), and VAT area.
In women, a lower A/L ratio was associated with larger adipocytes, increased macrophage content, higher TyG index, serum CRP levels, and VAT area. Multivariate models indicated that SAT inflammation and adipokine imbalance are predictive of VAT, and mediation models confirmed these findings. In contrast, ADIPO-IR was identified as the primary predictor of visceral fat content among men. These findings emphasize the importance of considering sex differences in the prevention and treatment strategies for metabolic diseases.
Keywords: adipose tissue dysfunction, adiposopathy, adiponectin, leptin, visceral fat