Identification of the determinants of susceptibility to high-fat diet-induced glucose intolerance using a new mouse model

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860300
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Nippon Medical School
• Principal Investigator: NAGAO Mototsugu 日本医科大学, 医学部, 助教 (10468762)
• Research Collaborator: YAGIHASHI Souroku ; INABA Wataru
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 選抜交配 / モデルマウス / 高脂肪食 / 耐糖能異常 / 摂食行動 / インスリン分泌能 / レプチン分泌能

Outline of Final Research Achievements

We have performed repetitive selective breeding of mice exhibiting different glucose tolerance after high-fat diet (HFD) feeding, and recently established 2 mouse lines with distinctively different susceptibilities (prone and resistant) to HFD-induced glucose intolerance (SDG-P and SDG-R, respectively). In the present study, we analyzed the differences in insulin secretory capacity and in feeding behavior between the 2 lines of mice to explore the hereditary predisposition to HFD-induced glucose intolerance. As compared to SDG-R mice, SDG-P mice showed lower glucose-induced insulin secretory capacity in vivo and in vitro (isolated islets) even before HFD feeding. In addition, SDG-P mice showed hyperphagia preceding the development of obesity under HFD feeding, and had lower plasma leptin levels as compared to SDG-R mice. In conclusion, hereditary insulin and leptin secretion may determine the susceptibility to HFD-induced glucose intolerance.

Free Research Field

実験病理学