PT  - JOURNAL ARTICLE
AU  - Alexis Maximilien Bachmann
AU  - Jean-David Morel
AU  - Gaby El Alam
AU  - Sandra Rodríguez-López
AU  - Tanes Imamura de lima
AU  - Ludger J.E. Goeminne
AU  - Giorgia Benegiamo
AU  - Maroun Bou Sleiman
AU  - Johan Auwerx
TI  - Genetic, metabolic, and molecular insights into the diverse outcomes of diet-induced obesity in mice
AID  - 10.1101/2021.09.02.458729
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.02.458729
4099  - http://biorxiv.org/content/early/2021/09/07/2021.09.02.458729.short
4100  - http://biorxiv.org/content/early/2021/09/07/2021.09.02.458729.full
AB  - Overweight and obesity are increasingly common public health issues worldwide, leading to a wide range of diseases from metabolic syndrome to steatohepatitis and cardiovascular diseases. While the increase in the prevalence of obesity is partly attributable to changes in lifestyle (i.e. increased sedentarity and changes in eating behaviour), the metabolic and clinical impacts of these obesogenic conditions varies between sexes and genetic backgrounds. The conception of personalised treatments of obesity and its complications require a thorough understanding of the diversity of responses to conditions such as high-fat diet intake. By analysing nine genetically diverse mouse strains, we show that much like humans, mice respond to high-fat diet in a genetic- and sex-dependent manner. Physiological and molecular responses to high-fat diet are associated with expression of genes involved in immunity and mitochondrial function. Finally, we find that mitochondrial function may explain part of the diversity of physiological responses. By exploring the complex interactions between genetics and metabolic phenotypes via gene expression and molecular traits, we shed light on the importance of genetic background and sex in determining metabolic outcomes. In addition to providing the community with an extensive resource for optimizing future experiments, our work serves as an exemplary design for more generalizable translational studies.Competing Interest StatementThe authors have declared no competing interest.