Date of Graduation

Spring 2016

Document Type

Honors Research Project

Degree Name

Bachelor of Science

Major

Natural Sciences - Divisional

Research Sponsor

Hazel Barton, Ph.D.

First Reader

Yoonkwang Lee, Ph.D.

Second Reader

Leah Shriver, Ph.D.

Abstract

The whole-body deletion of small heterodimer partner (SHP) in mice is associated with protection from diet-induced obesity and hepatic steatosis upon feeding of a western diet. This protection was reported to be mediated through decreases in hepatic gene expression for lipogenesis, as well as increases in gene expression for fatty acid oxidation. SHP has been known to regulate the expression of the CYP7A1 gene, encoding the rate-limiting enzyme for bile acid synthesis, thereby altering the bile acid pool. The effects of this altered bile acid profile on the gut microbiome are unknown, as some bacteria in the gut are responsible for bile acid metabolism while others are killed by the detergent effect of bile acids. This study shows that mice without SHP display a distinctly different microbiome from wild-type mice, characterized by a reduction of phylogenetic diversity and an increased abundance of the Bacteroidetes phylum with a proportional decrease in Firmicutes abundance. Cohousing mice led to increased microbiome similarity between genotypes, with a blunted reduction of phylogenetic diversity in SHP-/- mice. Furthermore, cohoused mice displayed reductions in the hepatic gene expression for synthesis of fatty acids, lipid droplets, and bile acids without altering fat and liver mass. These results may suggest a relationship between SHP and the microbiome in the development of diet-induced obesity but not hepatic steatosis.