The susceptibility to weight gain in male C57BL/6 mice fed high-fat diet is due to a small set of genes predominantly not expressed in the brain
8 affiliations
- 1Laboratory of Integrative Physiology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
- 2Institutes of Biomedical Sciences, Inner Mongolia University, Hohhot 010020, China
- 3Faculty of Space Technologies, Akademia Gorniczo-Hutnicza, University of Krakow, Krakow 30-059, Poland
- 4Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai 264005, China
- 5Institute of Health Sciences, China Medical University, Shenyang, Liaoning 110122, China
- 6Shenzhen Key laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- 7Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland AB24 2TZ, United Kingdom
- 8Faculty of Pharmaceutical Sciences Shenzhen, Shenzhen University of Advanced Technology, Shenzhen 518107, China
Abstract
Obesity results from a gene by environment interaction. Understanding the impacts of environmental factors like diet on body weight/fatness has been greatly facilitated by rodent models. We previously identified the responses of males of five mouse strains fed 30 different diets. Two of these strains showed much greater weight gain and two were resistant. Sixty-six marker SNPs in 57 genes were identified, which have a genetic motif across the four strains reflecting their protection or susceptibility to high-fat diet (HFD). We used two of these strains: C57BL/6 and BALB/c, in a classic approach of cross-breeding the strains, to generate a F1 generation, and then cross-breeding their offspring to generate an F2 population. The F2 males were fed HFD and phenotyped for body weight, fat mass, and energy intake and genotyped for the 66 SNPs. Body mass gain on HFD was influenced by 17 SNPs in 11 genes explaining 87% of the individual variation in weight gain. We then measured gene expression of these 11 genes in 16 tissues of male and female C57BL/6 and Balb/c mice when fed high- or low-fat diets, and in 6 tissues of mice exposed to different levels of calorie restriction, to map their expression profiles. The genes were widely expressed in a diversity of tissues including several not normally suspected to be important for fat storage regulation (e.g., testis, lungs, and spleen) with only four expressed predominantly in the hypothalamus. Body fat regulation is probably more complex than current models focused on the brain–adipose axis suppose.
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BibTeX
@article{wu2026susceptibility,
title = {{The susceptibility to weight gain in male C57BL/6 mice fed high-fat diet is due to a small set of genes predominantly not expressed in the brain}},
author = {Yingga Wu and Agata M. Rudolf and Lu Wang and Zhengjie Zhang and Chaoqun Niu and Fan Xia and Min Li and Anyongqi Wang and Davina Derous and Sharon E. Mitchell and Haoran Zhang and Yalin He and John R. Speakman},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2613656123},
url = {https://doi.org/10.1073/pnas.2613656123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The susceptibility to weight gain in male C57BL/6 mice fed high-fat diet is due to a small set of genes predominantly not expressed in the brain
AU - Yingga Wu
AU - Agata M. Rudolf
AU - Lu Wang
AU - Zhengjie Zhang
AU - Chaoqun Niu
AU - Fan Xia
AU - Min Li
AU - Anyongqi Wang
AU - Davina Derous
AU - Sharon E. Mitchell
AU - Haoran Zhang
AU - Yalin He
AU - John R. Speakman
PY - 2026
DA - 2026/10/20
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2613656123
UR - https://doi.org/10.1073/pnas.2613656123
AB - Obesity results from a gene by environment interaction. Understanding the impacts of environmental factors like diet on body weight/fatness has been greatly facilitated by rodent models. We previously identified the responses of males of five mouse strains fed 30 different diets. Two of these strains showed much greater weight gain and two were resistant. Sixty-six marker SNPs in 57 genes were identified, which have a genetic motif across the four strains reflecting their protection or susceptibility to high-fat diet (HFD). We used two of these strains: C57BL/6 and BALB/c, in a classic approach of cross-breeding the strains, to generate a F1 generation, and then cross-breeding their offspring to generate an F2 population. The F2 males were fed HFD and phenotyped for body weight, fat mass, and energy intake and genotyped for the 66 SNPs. Body mass gain on HFD was influenced by 17 SNPs in 11 genes explaining 87% of the individual variation in weight gain. We then measured gene expression of these 11 genes in 16 tissues of male and female C57BL/6 and Balb/c mice when fed high- or low-fat diets, and in 6 tissues of mice exposed to different levels of calorie restriction, to map their expression profiles. The genes were widely expressed in a diversity of tissues including several not normally suspected to be important for fat storage regulation (e.g., testis, lungs, and spleen) with only four expressed predominantly in the hypothalamus. Body fat regulation is probably more complex than current models focused on the brain–adipose axis suppose.
SN - 0027-8424
SN - 1091-6490
ER -