Increased Adipose Tissue Insulin Resistance in Metabolic Syndrome: Relationship to Circulating Adipokines

Background: Although hepatic insulin resistance has been documented in patients with metabolic syndrome using homeostasis model assessment of insulin resistance (HOMA-IR) as a measure, there is scanty data on adipose insulin resistance (Adipo-IR) and its relationship with the dysregulation of adipokines in metabolic syndrome. Thus, we examined whether Adipo-IR is increased in metabolic syndrome as well as its correlation with circulating adipokines. Methods: In 42 individuals including controls and participants with metabolic syndrome, we measured fasting plasma insulin and free fatty acids (FFA). Adipo-IR was calculated as the product of FFAxinsulin. We examined the association between Adipo-IR, metabolic syndrome variables, and circulating adipokines, including leptin, adiponectin, chemerin, omentin-1, and retinol-binding protein-4. Results: Adipo-IR was higher in metabolic syndrome (n=19; median 68.7 mmol/L center dot pmol/L; 25(th)-75(th) percentile, 50.0-104.7) compared to controls (n=23; 22.9 mmol/L center dot pmol/L; 6.8-36.1; P<0.0001), and this difference was similar following adjustments for waist circumference or body mass index (BMI). Adipo-IR correlated significantly with certain adipokines: Leptin, r=0.45, P=0.004; adiponectin, r=-0.33, Pr=0.55, P=0.0008; omentin-1, r=-0.46, P=0.04, and with all features of metabolic syndrome. Conclusions: Adipo-IR is increased in metabolic syndrome following adjustment for adiposity and may be an important biomarker of adipose tissue dysregulation, including adipokine secretion and a potential relevant therapeutic target.