Abstract
Different diets have distinct impacts on glucose homoeostasis, for which insulin sensitivity (IS) after a meal (postprandial IS) is highly relevant. Postprandial IS depends upon hepatic parasympathetic activation and glutathione content elevation. We tested the hypothesis that postprandial IS is compromised in high-fat diet (HFD)-induced obesity. Sprague-Dawley rats were fed a standard diet (STD, n 10), 1-week HFD (n 9) or 4-week HFD (n 8). IS was tested in postprandial state using the rapid IS test (RIST) before and after the blockade of the parasympathetic nerves (atropine, 1 mg/kg); parasympathetic-dependent IS was obtained from the difference between control and post-atropine RIST. Fasting IS was also assessed in the STD-fed rats (n 4) and 4-week HFD-fed rats (n 3) using the RIST. Whole-body fat and regional fat pads were heavier in the 1-week HFD-fed rats (79.8 (SE 7.9) and 23.7 (SE 1.0) g, respectively) or 4-week HFD-fed rats (106.5 (SE 6.1) and 30.1 (SE 1.4) g, respectively) than in the STD-fed rats (32.5 (SE 3.7) and 13.7 (SE 1.0) g, respectively; P < 0.001). Fasted-state IS was similar between the groups studied. Postprandial IS was higher in the STD-fed rats (185.8 (SE 5.6) mg glucose/kg body weight (bw)) than in both the 1-week HFD-fed rats (108.8 (SE 2.9) mg glucose/kg bw; P < 0.001) and 4-week HFD-fed rats (69.3 (SE 2.6) mg glucose/kg bw; P < 0.001). Parasympathetic-dependent IS was impaired in both HFD-fed groups (STD, 108.9 (SE 3.9) mg glucose/kg bw; 1-week HFD, 38.6 (SE 4.2) mg glucose/kg bw; 4-week HFD, 5.4 (SE 1.7) mg glucose/kg bw; P < 0.001). Total (postprandial) and parasympathetic-dependent IS correlated negatively with whole-body fat (R² 0.81 and 0.87) and regional adiposity (R² 0.85 and 0.79). In conclusion, fat accumulation induced by HFD is associated with postprandial insulin resistance, but not with fasting insulin resistance. HFD-associated postprandial insulin resistance is largely mediated by impairment of parasympathetic-dependent insulin action, which correlates with adiposity.
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