Page 22 - Y. Vascular biology

[Y. Vascular biology-15]

Gut microbiota and liver transcriptome underlying sexual

dimorphism of atherosclerosis in a hyperlipidemic diversity

outbred F1 mouse population

Myungsuk Kim¹˙², Nazmul Huda², Excel Que², Erik R. Gertz², Brian J. Bennett¹˙²˙*

¹Department of Nutrition, University of California, Davis, Davis 95616, United States, ²Obesity & Metabolism Unit,

USDA-ARS-Western Human Nutrition Research Center, Davis 95616, United States

Atherosclerosis is a complex multifactorial disease that develops through the interaction of various genetic and
environmental factors. Differences in atherosclerosis by sex have been well documented. However, how sex

influences the pathogenesis of atherosclerosis is unclear. We hypothesized that the association between gut
microbial profiles, liver transcriptome, and atherosclerosis demonstrates sexual dimorphism. In order to test this

hypothesis, we studied sexual dimorphism in cardio-metabolic traits, gut microbiota, and liver gene expression
using 470 hyperlipidemic Diversity Outbred (DO) mice. The results revealed the sexually dimorphic cardio-metabolic

traits, gut microbiota, and gene expression regardless of the genetic background. Different gut microbial diversity
and aortic lesion area-associated genera levels between sexes were associated with susceptibility to atherosclerosis.

Global gene expression analyses of liver tissue revealed inflammatory pathway and coagulation cascade in females
and mitochondrial biogenesis and steroid biosynthesis in males. To the best of our knowledge, this study suggests

the first example of complex interactions between sexually dimorphic traits, gut microbiota, and liver transcriptome
using DO-F1 mice.