Blockade of kinin B₁ receptor reverses plasma fatty acids composition changes and body and tissue fat gain in a rat model of insulin resistance

Aim: Kinin B₁ receptor (B₁R) contributes to insulin resistance through a mechanism involving oxidative stress. This study examined the effect of B₁R blockade on the changes in plasma fatty acids composition, body and tissue fat mass and adipose tissue inflammation that influence insulin resistance. Methods: Sprague-Dawley rats were fed with 10% D-glucose or tap water (Control) for 13 weeks and during the last week, rats were administered the B₁R antagonist SSR240612 (10 mg/kg/day, gavage) or vehicle. The following parameters were assessed: plasma fatty acids (by gas chromatography), body composition (by EchoMRI), metabolic hormone levels (by radioimmunoassay), expression of B₁R and inflammatory markers in adipose tissue (by Western blot and qRT-PCR). Results: Glucose feeding significantly increased plasma levels of glucose, insulin, leptin, palmitoleic acid (16:1n-7), oleic acid (18:1n-9), Δ6 and Δ9 desaturases while linoleic acid (18:2n-6), arachidonic acid (20:4n-6) and Δ5 desaturase were decreased. SSR240612 reduced plasma levels of insulin, glucose, the homeostasis model assessment index of insulin resistance, palmitoleic acid and n-7 family. Alterations of Δ5, Δ6 and Δ9 desaturases were normalized by SSR240612. The B₁R antagonist also reversed the enhancing effect of glucose feeding on whole body and epididymal fat mass and on the expression of macrophage CD68, interleukin-1β, tumour necrosis factor-α and inducible nitric oxide synthase in retroperitoneal adipose tissue. B₁R protein and mRNA were not detected in retroperitoneal adipose tissue. Conclusion: Insulin resistance in glucose-fed rats is associated with low state inflammation in adipose tissue and plasma fatty acids changes which are reversed by B₁R blockade. These beneficial effects may contribute to insulin sensitivity improvement and the prevention of obesity.