High-fat-diet induced development of increased fasting glucose levels and impaired response to intraperitoneal glucose challenge in the collaborative cross mouse genetic reference population

BMC Genetics

Research Article

Hanifa J. Abu-Toamih Atamni¹  Fuad A. Iraqi¹  Morris Soller²  Richard Mott³ 

[1] Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, 69978, Tel-Aviv, Israel;Hebrew University, Jerusalem, Israel;University of Oxford, Oxford, UK;

关键词: Type 2 diabetes (T2D);    Metabolic syndrome;    Obesity;    High fat diet (HFD);    Sex effects;    Collaborative Cross mouse reference population;    Heritability;    Coefficient of genetic variation;   

DOI  :  10.1186/s12863-015-0321-x

 received in 2015-08-19, accepted in 2015-12-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe prevalence of Type 2 Diabetes (T2D) mellitus in the past decades, has reached epidemic proportions. Several lines of evidence support the role of genetic variation in the pathogenesis of T2D and insulin resistance. Elucidating these factors could contribute to developing new medical treatments and tools to identify those most at risk. The aim of this study was to characterize the phenotypic response of the Collaborative Cross (CC) mouse genetic resource population to high-fat diet (HFD) induced T2D-like disease to evluate its suitability for this purpose.ResultsWe studied 683 mice of 21 different lines of the CC population. Of these, 265 mice (149 males and 116 females) were challenged by HFD (42 % fat); and 384 mice (239 males and145 females) of 17 of the 21 lines were reared as control group on standard Chow diet (18 % fat). Briefly, 8 week old mice were maintained on HFD until 20 weeks of age, and subsequently assessed by intraperitoneal glucose tolerance test (IPGTT). Biweekly body weight (BW), body length (BL), waist circumstance (WC), and body mass index (BMI) were measured. On statistical analysis, trait measurements taken at 20 weeks of age showed significant sex by diet interaction across the different lines and traits. Consequently, males and females were analyzed, separately. Differences among lines were analyzed by ANOVA and shown to be significant (P <0.05), for BW, WC, BMI, fasting blood glucose, and IPGTT-AUC. We use these data to infer broad sense heritability adjusted for number of mice tested in each line; coefficient of genetic variation; genetic correlations between the same trait in the two sexes, and phenotypic correlations between different traits in the same sex.ConclusionsThese results are consistent with the hypothesis that host susceptibility to HFD-induced T2D is a complex trait and controlled by multiple genetic factors and sex, and that the CC population can be a powerful tool for genetic dissection of this trait.

【 授权许可】

CC BY   
© Atamni et al. 2015