Expression profiling by high throughput sequencing
Summary
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. Results: 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 and supercomplex assembly 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.
Overall design
Design: This RNAseq dataset covers the response to HFD in the mouse liver of 9 mouse strains (PWK/PhJ, CAST/EiJ, WSB/EiJ, NZO/HlLt, JNOD/ShiLtJ, 129S1/SvImJ, A/J, DBA/2J, C57BL/6J). 6 female and 6 male animals from 9 inbred mouse strains were fed with either a chow diet (CD) or high-fat diet (HFD) from the age of 8 to 21 weeks and various metabolic and fitness phenotypes were measured. Eight of these strains are known as the founders of the Collaborative Cross (CC) and Diversity Outbred (DO) populations, with the addition of the DBA/2J strain.
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