Blockade of kinin B(1) receptor reverses plasma fatty acids composition changes and body and tissue fat gain in a rat model of insulin resistance.

Abstract

AIM:

Kinin B(1) receptor (B(1) R) contributes to insulin resistance through a mechanism involving oxidative stress. This study examined the effect of B(1) R 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 B(1) R 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 B(1) R 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 B(1) R 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. B(1) R 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 B(1) R blockade. These beneficial effects may contribute to insulin sensitivity improvement and the prevention of obesity.

• Authors: J P Dias, R Couture
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 14 Issue 3 Pg. 244-53 (Mar 2012) ISSN: 1463-1326 [Electronic] England
• PMID: 22023455 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• 2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide
• Blood Glucose
• Bradykinin B1 Receptor Antagonists
• Dioxoles
• Fatty Acids
• Receptor, Bradykinin B1
• Sulfonamides
• Glucose

Topics

• Adipose Tissue (drug effects, metabolism)
• Animals
• Blood Glucose (metabolism)
• Body Composition
• Bradykinin B1 Receptor Antagonists
• Dioxoles (administration & dosage, pharmacology)
• Disease Models, Animal
• Fatty Acids (blood)
• Glucose (administration & dosage, pharmacology)
• Inflammation (metabolism)
• Insulin Resistance
• Male
• Obesity (prevention & control)
• Rats
• Rats, Sprague-Dawley
• Receptor, Bradykinin B1 (metabolism)
• Sulfonamides (administration & dosage, pharmacology)