Genes, Diet, and Body Weight (in Mice)

What affects body weight? Is it genetic factors or is it diet or is it both?

Our group collaborated with Jake Lusis’ group on a mouse study led by Brian Parks that aimed to address this question and the results were published in Cell Metabolism (10.1016/j.cmet.2012.12.007). From our group, Emrah Kostem contributed to the study. The study received a lot of press coverage including Science News, Huffington Post, and

It turns out that not only do both genes and diet contribute to body weight, a significant factor is the interaction between genes and diet. Some strains of mice gained a significant amount of weight on a high fat diet, whiles others did not. These types of interactions, or “gene-by-environment” interactions are if great interest to our group and we are working on several projects on this topic.

What is also exciting about this study is that it is the first published report of our second round of studies using the Hybrid Mouse Diversity Panel (HMDP) (10.1007/s00335-012-9411-5). The first round of studies reported associations for lipids(10.1101/gr.099234.109), bone traits (10.1371/journal.pgen.1002038), and fear conditioning (10.1186/1752-0509-5-43). This next round focuses on gene-by-environment interactions. The HMDP is now no longer just a UCLA project. Now several groups at other institutions including USC, UC Berkeley and University of Washington are also involved in HMDP studies.


Full Citation:

Parks, B.W., Nam, E., Org, E., Kostem, E., Norheim, F., Hui, S.T., Pan, C., Civelek, M., Rau, C.D., Bennett, B.J., Mehrabian, M., Ursell, L.K., He, A., Castellani, L.W., Zinker, B., Kirby, M., Drake, T.A., Drevon, C.A., Knight, R., Gargalovic, P., Kirchgessner, T., Eskin, E. & Lusis, A.J., 2013, Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice, Cell Metab, 17(1), pp. 141-52.


Obesity is a highly heritable disease driven by complex interactions between genetic and environmental factors. Human genome-wide association studies (GWAS) have identified a number of loci contributing to obesity; however, a major limitation of these studies is the inability to assess environmental interactions common to obesity. Using a systems genetics approach, we measured obesity traits, global gene expression, and gut microbiota composition in response to a high-fat/high-sucrose (HF/HS) diet of more than 100 inbred strains of mice. Here we show that HF/HS feeding promotes robust, strain-specific changes in obesity that are not accounted for by food intake and provide evidence for a genetically determined set point for obesity. GWAS analysis identified 11 genome-wide significant loci associated with obesity traits, several of which overlap with loci identified in human studies. We also show strong relationships between genotype and gut microbiota plasticity during HF/HS feeding and identify gut microbial phylotypes associated with obesity.