Rosiglitazone Improves Insulin Sensitivity and Baroreflex Gain in Rats with Diet‐induced Obesity

Abstract

Obesity decreases baroreflex gain (BRG); however, the mechanisms are unknown. We tested the hypothesis that the impaired BRG is related to the concurrent insulin resistance. Male SD rats (~250 g) fed a high fat diet (HFD, 33% kcal fat) diverged into obesity‐prone (OP; top tertile of weight gain) and obesity‐resistant (OR; bottom tertile of weight gain) groups after 2 weeks. Subsequently, the OP and OR rats, as well as control (CON) rats fed a standard diet, were treated daily by gavage for 2–3 weeks with the insulin sensitizing drug, rosiglitazone (ROSI, 6 mg/kg), or its vehicle. Compared to conscious OR and CON rats, OP rats exhibited reduced BRG (in bpm/mmHg: OP, 2.9±0.1; OR, 4.0±0.2; CON, 3.9±0.2; n=5 per group; P<0.05) and insulin sensitivity (IS, in mg/kg·min: OP, 6.8±0.9; OR, 22.2±1.2; CON, 17.7±0.8; n=8 per group; P<0.05), and the decreases in IS and BRG were well correlated (r2=0.44; P<0.01). In OP rats (n=5), ROSI increased IS (to 16.0±1.5 mg/kg·min; P<0.01) and BRG (to 5.3±0.7 bpm/mmHg; P<0.05), but not in CON rats. In OR rats (n=5), ROSI improved (P<0.05) BRG (to 5.6±0.4 bpm/mmHg), but not IS. In addition, in OP and OR rats, for a given level of IS, ROSI produced further increments in BRG (ANCOVA, P<0.005). In conclusion, with diet‐induced obesity in rats, the reductions in BRG and IS share common mechanisms. Moreover, ROSI appears to improve BRG in rats fed a HFD by an additional mechanism unrelated to its effect to increase IS. (Supported by AHA and HL088552)