title: 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.
abstract: 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 (~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 HFFD (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 HFFD 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 HFFD than in CTR. It was also attributable to lower net hepatic glucose uptake (NHGU) in the HFFD group (5.5 ± 3.9 μmol · kg(-1) · min(-1)) compared to the CTR group (26.6 ± 7.0 μmol · kg(-1) · min(-1)), resulting in lower hepatic glycogen synthesis (GSYN) in the HFFD group (10.8 ± 5.4 μmol · kg(-1) · min(-1)) than in the CTR group (30.4 ± 7.0 μmol · kg(-1) · min(-1)). HFFD also displayed aberrant suppression of lipolysis by insulin. In conclusion, HFFD 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 HFFD for 8 wk.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Katie Colbert
authors.initials: KC
authors.lastname: Coate
authors.forename: Guillaume
authors.initials: G
authors.lastname: Kraft
authors.forename: Margaret
authors.initials: M
authors.lastname: Lautz
authors.forename: Marta
authors.initials: M
authors.lastname: Smith
authors.forename: Doss W
authors.initials: DW
authors.lastname: Neal
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000409:Alanine / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose; D001798:Blood Proteins; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage*; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D010180:Pancreatectomy; D011506:Proteins / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D001798:Blood Proteins; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids; D011506:Proteins; D005632:Fructose; D019344:Lactic Acid; D006003:Glycogen; D005947:Glucose; D000409:Alanine; D005990:Glycerol