A High-Fat, High-Fructose Diet Accelerates Nutrient Absorption and Impairs Net Hepatic Glucose Uptake in Response to a Mixed Meal in Partially Pancreatectomized Dogs

The aim of this study was to elucidate the impact of a high-fat, high-fructose diet (HFFD; fat, 52%; fructose, 17%), in the presence of a partial (similar to 65%) pancreatectomy (PPx), on the response of the liver and extrahepatic tissues to an orally administered, liquid mixed meal. Adult male dogs were fed either a nonpurified, canine control diet (CTR; fat, 26%; no fructose; n = 5) or a HEED (n = 5) for 8 wk. Diets were provided in a quantity to maintain neutral or positive energy balance in CTR or HFFD, respectively. Dogs underwent a sham operation or PPx at wk 0, portal and hepatic vein catheterization at wk 6, and a mixed meal test at wk 8. Postprandial glucose concentrations were significantly greater in the HEED group (14.5 +/- 2.0 mmol/L) than in the CTR group (9.2 +/- 0.5 mmol/L). Impaired glucose tolerance in HFFD was due in part to accelerated gastric emptying and glucose absorption, as indicated by a more rapid rise in arterial plasma acetaminophen and the rate of glucose output by the gut, respectively, in HEED than in CTR. It was also attributable to lower net hepatic glucose uptake (NHGU) in the HEED group (5.5 +/- 3.9 mu mol.kg(-1).min(-1)) compared to the CTR group (26.6 +/- 7.0 mu mol.kg(-1).min(-1)), resulting in lower hepatic glycogen synthesis (GSYN) in the HFFD group (10.8 +/- 5.4 mu mol.kg(-1).min(-1)) than in the CTR group (30.4 +/- 7.0 mu mol.kg(-1).min(-1)). HFFD also displayed aberrant suppression of lipolysis by insulin. In conclusion, HEED feeding accelerates gastric emptying and diminishes NHGU and GSYN, thereby impairing glucose tolerance following a mixed meal challenge. These data reveal a constellation of deleterious metabolic consequences associated with consumption of a HEED for 8 wk. J. Nutr. 141: 1643-1651, 2011.