High-fat diet and oral infection induced type 2 diabetes and obesity development under different genetic backgrounds

Iqbal M. Lone, Nadav Ben Nun, Aya Ghnaim, Arne S. Schaefer, Yael Houri-Haddad, Fuad A. Iraqi*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    8 Scopus citations


    Background: Type 2 diabetes (T2D) is an adult-onset and obese form of diabetes caused by an interplay between genetic, epigenetic, and environmental components. Here, we have assessed a cohort of 11 genetically different collaborative cross (CC) mouse lines comprised of both sexes for T2D and obesity developments in response to oral infection and high-fat diet (HFD) challenges. Methods: Mice were fed with either the HFD or the standard chow diet (control group) for 12 weeks starting at the age of 8 weeks. At week 5 of the experiment, half of the mice of each diet group were infected with Porphyromonas gingivalis and Fusobacterium nucleatum bacteria strains. Throughout the 12-week experimental period, body weight (BW) was recorded biweekly, and intraperitoneal glucose tolerance tests were performed at weeks 6 and 12 of the experiment to evaluate the glucose tolerance status of mice. Results: Statistical analysis has shown the significance of phenotypic variations between the CC lines, which have different genetic backgrounds and sex effects in different experimental groups. The heritability of the studied phenotypes was estimated and ranged between 0.45 and 0.85. We applied machine learning methods to make an early call for T2D and its prognosis. The results showed that classification with random forest could reach the highest accuracy classification (ACC = 0.91) when all the attributes were used. Conclusion: Using sex, diet, infection status, initial BW, and area under the curve (AUC) at week 6, we could classify the final phenotypes/outcomes at the end stage of the experiment (at 12 weeks).

    Original languageAmerican English
    Pages (from-to)131-145
    Number of pages15
    JournalAnimal Models and Experimental Medicine
    Issue number2
    StatePublished - Apr 2023

    Bibliographical note

    Publisher Copyright:
    © 2023 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.


    • collaborative cross
    • genetic covariance
    • heritability
    • high-fat diet
    • machine learning
    • mouse model
    • obesity
    • type 2 diabetes


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