title: Differential effects of hypercaloric choice diets on insulin sensitivity in rats.
abstract: We showed previously that rats on a free-choice high-fat, high-sugar (fcHFHS) diet become rapidly obese and develop glucose intolerance within a week. Interestingly, neither rats on a free-choice high-fat diet (fcHF), although equally obese and hyperphagic, nor rats on a free-choice high-sugar (fcHS) diet consuming more sugar water, develop glucose intolerance. Here, we investigate whether changes in insulin sensitivity contribute to the observed glucose intolerance and whether this is related to consumption of saturated fat and/or sugar water. Rats received either a fcHFHS, fcHF, fcHS or chow diet for one week. We performed a hyperinsulinemic-euglycemic clamp with stable isotope dilution to measure endogenous glucose production (EGP; hepatic insulin sensitivity) and glucose disappearance (Rd; peripheral insulin sensitivity). Rats on all free-choice diets were hyperphagic, but only fcHFHS-fed rats showed significantly increased adiposity. EGP suppression by hyperinsulinemia in fcHF-fed and fcHFHS-fed rats was significantly decreased compared with chow-fed rats. One week fcHFHS diet also significantly decreased Rd. Neither EGP suppression nor Rd was affected in fcHS-fed rats. Our results imply that, short-term fat feeding impaired hepatic insulin sensitivity, whereas short-term consumption of both saturated fat and sugar water impaired hepatic and peripheral insulin sensitivity. The latter likely contributed to glucose intolerance observed previously. In contrast, overconsumption of only sugar water affected insulin sensitivity slightly, but not significantly, in spite of similar adiposity as fcHF-fed rats and higher sugar intake compared with fcHFHS-fed rats. These data imply that the palatable component consumed plays a role in the development of site-specific insulin sensitivity.
authors.affiliation: Department of Endocrinology and MetabolismAcademic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: Charlene
authors.initials: C
authors.lastname: Diepenbroek
authors.affiliation: Department of Endocrinology and MetabolismAcademic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: Leslie
authors.initials: L
authors.lastname: Eggels
authors.affiliation: Department of Clinical ChemistryLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: Mariëtte T
authors.initials: MT
authors.lastname: Ackermans
authors.affiliation: Department of Endocrinology and MetabolismAcademic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Endocrinology and MetabolismAcademic Medical Center, University of Amsterdam, the Netherlands.|Hypothalamic Integration MechanismsNetherlands Institute for Neuroscience, Amsterdam, the Netherlands.
authors.forename: Andries
authors.initials: A
authors.lastname: Kalsbeek
authors.affiliation: Department of Endocrinology and MetabolismAcademic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: Mireille J
authors.initials: MJ
authors.lastname: Serlie
authors.affiliation: Department of Endocrinology and MetabolismAcademic Medical Center, University of Amsterdam, the Netherlands s.e.lafleur@amc.uva.nl.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: la Fleur
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002755:Choice Behavior / Q000502:physiology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D002149:Energy Intake / Q000502:physiology*; D005518:Food Preferences / Q000502:physiology*; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000209:etiology* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose
keywords: Wistar rats; free-choice diet; insulin sensitivity; obesity