title: Energy restriction combined with dipeptidyl peptidase-4 inhibitor exerts neuroprotection in obese male rats.
abstract: Dipeptidyl peptidase-4 (DDP-4) inhibitors and energy restriction (ER) are widely used to treat insulin resistance and type 2 diabetes mellitus. However, the effects of ER or the combination with vildagliptin on brain insulin sensitivity, brain mitochondrial function, hippocampal synaptic plasticity and cognitive function in obese insulin-resistant rats have never been investigated. We hypothesised that ER with DDP-4 inhibitor exerts better efficacy than ER alone in improving cognition in obese insulin-resistant male rats by restoring brain insulin sensitivity, brain mitochondrial function and hippocampal synaptic plasticity. A total of twenty-four male Wistar rats were divided into two groups and fed either a normal diet or a high-fat diet (HFD) for 12 weeks. At week 13, the HFD rats were divided into three subgroups (n6/subgroup) to receive one of the following treatments: vehicle, ER (60 % of energy received during the previous 12 weeks) or ER plus vildagliptin (3 mg/kg per d, p.o.) for 4 weeks. At the end of the treatment, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity and brain mitochondrial function were determined. We found that HFD-fed rats demonstrated weight gain with peripheral insulin resistance, dyslipidaemia, oxidative stress, brain insulin resistance, impaired brain mitochondrial function and cognitive dysfunction. Although HFD-fed rats treated with ER and ER plus vildagliptin showed restored peripheral insulin sensitivity and improved lipid profiles, only ER plus vildagliptin rats had restored brain insulin sensitivity, brain mitochondrial function, hippocampal synaptic plasticity and cognitive function. These findings suggest that only a combination of ER with DPP-4 inhibitor provides neuroprotective effects in obese insulin-resistant male rats.
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.|Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Hiranya
authors.initials: H
authors.lastname: Pintana
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.|Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Pongpan
authors.initials: P
authors.lastname: Tanajak
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.|Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Wasana
authors.initials: W
authors.lastname: Pratchayasakul
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.|Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Piangkwan
authors.initials: P
authors.lastname: Sa-Nguanmoo
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.|Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Titikorn
authors.initials: T
authors.lastname: Chunchai
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.|Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Pattarapong
authors.initials: P
authors.lastname: Satjaritanun
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.|Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Linlada
authors.initials: L
authors.lastname: Leelarphat
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.|Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.|Department of Oral Biology and Diagnostic Science, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
keywords: Brain mitochondrial functions; Cognitive functions; Energy restriction; Hippocampal synaptic plasticity; Obese insulin-resistant rats; Vildagliptin