Free Fatty Acid-Induced Insulin Resistance in the Obese Is Not Prevented by Rosiglitazone Treatment

• Published in: The journal of clinical endocrinology and metabolism 2005-09, Vol.90 (9), p.5058-5063
• Main Authors: Dhindsa, Sandeep, Tripathy, Devjit, Sanalkumar, Nishanth, Ravishankar, Shreyas, Ghanim, Husam, Aljada, Ahmad, Dandona, Paresh
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; C-Reactive Protein - antagonists & inhibitors; Drug Combinations; Emulsions; Endocrinopathies; Fatty Acids, Nonesterified - antagonists & inhibitors; Fatty Acids, Nonesterified - blood; Female; Fundamental and applied biological sciences. Psychology; Glucose Clamp Technique; Heparin - administration & dosage; Humans; Infusion Pumps; Insulin Resistance; Male; Medical sciences; Middle Aged; Obesity - drug therapy; Obesity - physiopathology; Serum Amyloid A Protein - antagonists & inhibitors; Thiazolidinediones - therapeutic use; Triglycerides - administration & dosage; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2005-0223

Objective: Elevation of free fatty acids (FFAs) by the infusion of triglyceride-heparin emulsion infusion (TG-Hep) causes insulin resistance (IR). We examined the effect of insulin sensitizer (rosiglitazone) on FFA-induced IR. Design: Nine obese subjects underwent a 6-h infusion of TG-Hep before and after 6 wk of rosiglitazone (8 mg/d) treatment. Hyperinsulinemic euglycemic clamps were performed during 0–2 and 4–6 h of TG-Hep. Results: After rosiglitazone for 6 wk, fasting FFA concentration fell, but not significantly (489 ± 63 at 0 wk; 397 ± 58 μmol/liter at 6 wk; P = 0.16), whereas C-reactive protein (4.26 ± 0.95 at 0 wk; 2.03 ± 0.45 μg/ml at 6 wk) and serum amyloid A (17.36 ± 4.63 at 0 wk; 8.77 ± 1.63 μg/ml at 6 wk) decreased significantly. At 0 wk, TG-Hep infusion caused a decrease in glucose infusion rate (GIR) from 4.49 ± 0.95 mg/kg·min to 3.02 ± 0.59 mg/kg·min (P = 0.018). Rosiglitazone treatment resulted in an increase in baseline GIR to 6.29 ± 0.81 mg/kg·min (P = 0.03 vs. 0 wk), which decreased to 4.52 ± 0.53 mg/kg·min (P = 0.001) after 6 h of TG-Hep infusion. The decrease in GIR induced by TG-Hep infusion was similar before and after rosiglitazone therapy [1.47 ± 0.50 vs. 1.77 0.3 mg/kg·min (28.9 ± 6.5 vs. 26.4 ± 3.7%); P = 0.51]. The rise in FFAs and triglycerides after TG-Hep infusion was significantly lower at 6 wk (P = 0.006 for FFAs; P = 0.024 for triglycerides). Conclusions: We conclude that rosiglitazone: 1) causes a significant increase in GIR; 2) induces a decrease in inflammatory mediators, C-reactive protein, and serum amyloid A; 3) decreases the rise in FFAs and triglycerides after TG-Hep infusion; and 4) does not prevent FFA-induced IR.