title: High-fat diet results in postprandial insulin resistance that involves parasympathetic dysfunction.
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.
authors.affiliation: Department of Biochemistry, Faculdade de Ciências Médicas (FCM), Universidade Nova de Lisboa (UNL), Campo Martires da Patria, 130, 1169-056 Lisboa, Portugal.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Afonso
authors.forename: W Wayne
authors.initials: WW
authors.lastname: Lautt
authors.forename: Josh
authors.initials: J
authors.lastname: Schafer
authors.forename: Dallas J
authors.initials: DJ
authors.lastname: Legare
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Oliveira
authors.forename: M Paula
authors.initials: MP
authors.lastname: Macedo
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019518:Postprandial Period; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D005978:Glutathione