title: Reduced cell proliferation and neuroblast differentiation in the dentate gyrus of high fat diet-fed mice are ameliorated by metformin and glimepiride treatment.
abstract: We investigated the effects of a high-fat diet (HFD) and the subsequent treatment of metformin (met) and glimepiride (glim), which are widely prescribed for type 2 diabetes, on cell proliferation and neuroblast differentiation using Ki67 and doublecortin (DCX) immunohistochemistry, respectively. Animals were fed low-fat diet (LFD) or HFD for 8 weeks. After 5 weeks of the HFD treatment, met alone or met + glim was administered orally once a day for 3 weeks. Body weight and food intake were much higher in the HFD + vehicle-treated group than the LFD-treated group. The administration of met or met + glim to the HFD-treated group resulted in a decrease in weight gain and food intake. Ki67-immunoreactive ((+)) nuclei, DCX(+) neuroblasts and brain-derived neurotrophic factor (BDNF) protein levels were markedly decreased in the dentate gyrus (DG) of the HFD + vehicle-treated group compared to the LFD-treated group. The administration of met or met + glim to the HFD-treated group prevented the reduction of Ki67(+) nuclei, DCX(+) neuroblasts, BDNF levels in the DG. The intraventricular injection of K252a (a BDNF receptor blocker) to the HFD-treated group treated met or met + glim distinctively lowered the reduction of cell proliferation and neuroblast differentiation induced by HFD. These results suggest that a HFD significantly reduces cell proliferation and neuroblast differentiation by reducing BDNF levels and these effects are ameliorated by treatment with met or met + glim.
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.forename: Woosuk
authors.initials: W
authors.lastname: Kim
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Nam
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004435:Eating / Q000187:drug effects; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009479:Neuropeptides / Q000096:biosynthesis; D020813:Receptor, trkB / Q000037:antagonists & inhibitors; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D013453:Sulfonylurea Compounds; C057619:glimepiride; D008687:Metformin; D020813:Receptor, trkB