title: Exercise Does Not Protect against Peripheral and Central Effects of a High Cholesterol Diet GivenAd libitumin Old ApoE-/-Mice.
abstract: Aim:Advanced atherosclerosis increases inflammation and stroke risk in the cerebral vasculature. Exercise is known to improve cardio-metabolic profiles when associated with a caloric restriction, but it remains debated whether it is still beneficial without the dietary control. The aim of this study was to determine both the peripheral and central effects of exercise training combined with a cholesterol-rich diet givenad libitumin old ApoE-/-mice.Methods: Forty-five-weeks old obese ApoE-/-mice fed with a high cholesterol dietad libitumwere divided into Exercise-trained (EX; running wheel free access) and Sedentary (SED) groups. Insulin tolerance and brain imaging were performed before and after the twelve-weeks training. Tissue insulin resistance, oxidative stress, and inflammation markers in plasma, aorta, and brain were then assessed.Results: In EX ApoE-/-mice, no beneficial effect of exercise was observed on weight, abdominal fat, metabolic parameters, oxidative stress, or inflammation compared to SED. Despite the regular exercise training in ApoE-/-EX mice (mean of 12.5 km/week during 12 weeks), brain inflammation imaging score was significantly associated with increased blood brain barrier (BBB) leakage evaluated by imaging follow-up (r2= 0.87;p= 0.049) with a faster evolution compared to SED ApoE-/-mice.Conclusion: We conclude that in a context of high cardio-metabolic risk, exercise does not provide any protective effect in old ApoE-/-animals under high cholesterol diet givenad libitum. Peripheral (insulin sensitivity and oxidative/inflammatory status) but also central features (BBB preservation and protection against inflammation) did not show any benefits of exercise. Indeed, there was a fast induction of irreversible brain damage that was more pronounced in exercise-trained ApoE-/-mice.
authors.affiliation: Univ Lyon, CarMeN Laboratory, Institut National de la Santé et de la Recherche Médicale U1060, INRA U1397, Université Lyon 1, INSA Lyon, F-69600 Oullins, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Di Cataldo
authors.affiliation: Univ Lyon, CarMeN Laboratory, Institut National de la Santé et de la Recherche Médicale U1060, INRA U1397, Université Lyon 1, INSA Lyon, F-69600 Oullins, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Géloën
authors.affiliation: CERMEP-Imagerie Du Vivant Lyon, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Langlois
authors.affiliation: Lyon Neuroscience Research Center, Centre National de la Recherche Scientifique UMR5292, Institut National de la Santé et de la Recherche Médicale, University Lyon 1 Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Chauveau
authors.affiliation: Laboratoire Imagerie Moléculaire In vivo, UMR 1023 Institut National de la Santé et de la Recherche Médicale /CEA/Université Paris Sud - ERL 9218 Centre National de la Recherche Scientifique, CEA/I2BM/SHFJ Orsay, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Thézé
authors.affiliation: Centre National de la Recherche Scientifique UMR 5220, Institut National de la Santé et de la Recherche Médicale U.1060 (CREATIS), University Claude Bernard Lyon1 INSA de Lyon, France.
authors.forename: Violaine
authors.initials: V
authors.lastname: Hubert
authors.affiliation: Centre National de la Recherche Scientifique UMR 5220, Institut National de la Santé et de la Recherche Médicale U.1060 (CREATIS), University Claude Bernard Lyon1 INSA de Lyon, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Wiart
authors.affiliation: University of Lyon, University Lyon 1, Laboratoire Inter-Universitaire de Biologie de la Motricité (EA647) Villeurbanne, France.
authors.forename: Erica N
authors.initials: EN
authors.lastname: Chirico
authors.affiliation: Univ Lyon, CarMeN Laboratory, Institut National de la Santé et de la Recherche Médicale U1060, INRA U1397, Université Lyon 1, INSA Lyon, F-69600 Oullins, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rieusset
authors.affiliation: Univ Lyon, CarMeN Laboratory, Institut National de la Santé et de la Recherche Médicale U1060, INRA U1397, Université Lyon 1, INSA Lyon, F-69600 Oullins, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.affiliation: University of Lyon, University Lyon 1, Laboratoire Inter-Universitaire de Biologie de la Motricité (EA647) Villeurbanne, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pialoux
authors.affiliation: Univ Lyon, CarMeN Laboratory, Institut National de la Santé et de la Recherche Médicale U1060, INRA U1397, Université Lyon 1, INSA Lyon, F-69600 Oullins, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Canet-Soulas
keywords: atherosclerosis; neuroinflammation imaging; overfeeding; oxidative stress; physical activity