title: Impaired glucose and lipid metabolism in ageing aryl hydrocarbon receptor deficient mice.
abstract: Disturbed homeostasis of glucose and lipid metabolism are dominant features of the so-called metabolic syndrome (MetS) and can increase the risk for the development of type 2 diabetes (T2D), a severe metabolic disease. T2D prevalence increases with age. The aryl hydrocarbon receptor (AHR) is a sensor of small molecules including dietary components. AHR has been identified as potential regulator of glucose homeostasis and lipid metabolism. Epidemiologically, exposure to xenobiotic AHR ligands such as polycyclic aromatic hydrocarbons is linked to T2D. We assess here the potential role of the AHR in disturbances of glucose and lipid metabolism in young (age 2-5 months) and old (age > 1,5 years) AHR-deficient (AHR KO) mice. Fasted young wildtype (WT) and AHR-KO mice displayed similar blood glucose kinetics after challenge with intra-peritoneal glucose injection. However, old AHR-KO mice showed lower tolerance than WT to i.p. administered glucose, i.e. glucose levels rose higher and returned more slowly to normal levels. Old mice had overall higher insulin levels than young mice, and old AHR-KO had a somewhat disturbed insulin kinetic in the serum after glucose challenge. Surprisingly, young AHR-KO mice had significantly lower triglycerides, cholesterol, high density lipoprotein values than WT, i.e., a dyslipidemic profile. With ageing, AHR-KO and WT mice did not differ in these lipid levels, except for slightly reduced levels of triglycerides and cholesterol. In conclusion, our findings in AHR KO mice suggest that AHR expression is relevant for the maintenance of glucose and lipid homeostasis in old mice.
authors.affiliation: Leibniz-Research Institute for Environmental Medicine, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Biljes
authors.affiliation: Leibniz-Research Institute for Environmental Medicine, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Hammerschmidt-Kamper
authors.affiliation: Leibniz-Research Institute for Environmental Medicine, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany ; University of Essen, Institute for Molecular Biology, Hufelandstr. 55, 45147 Essen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kadow
authors.affiliation: Deutsche Sporthochschule Köln, Institut für Kreislaufforschung und Sportmedizin, Am Sportpark Müngersdorf 6, 50933 Köln, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Diel
authors.affiliation: Deutsche Sporthochschule Köln, Institut für Kreislaufforschung und Sportmedizin, Am Sportpark Müngersdorf 6, 50933 Köln, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Weigt
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Auf´m Hennekamp 65, 40225 Düsseldorf, Germany ; German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Burkart
authors.affiliation: Leibniz-Research Institute for Environmental Medicine, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Esser
keywords: AHR; diet; dyslipidemia; metabolic syndrome; senescence