Date

2017

Department or Program

Neuroscience

Primary Wellesley Thesis Advisor

Marc Tetel

Abstract

The steroid hormone, 17b-Estradiol (E2), mediates a variety of functions including reproduction and metabolism. For example, due to lower levels of circulating estrogens, postmenopausal women tend to gain fat weight, which increases their risk for diseases such as heart disease and Type II diabetes. Ovariectomized mice, whose endogenous source of E2 are removed, become obese when fed a high-fat diet (HFD). Our lab and others have shown that E­2 treatment prevents this HFD-induced obesity in female mice. The protein hormone leptin, which is encoded by the ob gene and released from adipocytes, is also involved in metabolism and regulates appetite through signaling to the brain when the animal is satiated. Mice with mutations in the ob gene (ob/ob) are unable to produce leptin and become obese and diabetic. The present experiment investigates the interaction between E2 and leptin in the regulation of the gut microbiome in female ob/ob mice fed a HFD. ob/ob (obese) mice and heterozygote controls (Het; lean) were ovariectomized and implanted with a capsule that contained either E­2 or oil (Vehicle control; Veh). The mice were fed a standard diet for four days and then a HFD for thirty-one days. During this period, food intake and weights were tracked. Both Het E­2 and ob/ob E2 mice weighed less and gained less weight than their Veh counterparts. Additionally, ob/ob mice gained less weight than Het mice even though ob/ob mice had higher food intake than Het mice. In order to compare the gut microbial composition between groups, fecal samples were collected then sequenced for the 16S rRNA gene. The ob/ob genotype and E2 treatment were associated with lower gut microbial diversity. ob/ob mice had lower species richness than Het mice while E2 treated mice had lower species evenness than Veh mice. Additionally, E2 treated mice had higher abundances of the phylum Bacteroidetes and lower abundances of phyla Firmicutes compared to Veh mice. ob/ob mice had lower abundances of the phylum Actinobacteria and the class Clostridia (phylum Firmicutes) compared to Het mice. These results demonstrated that both E2 treatment and ob/ob genotype modulate the gut microbiome of female mice fed a HFD. Understanding the important role of E2 and leptin in modulating the gut microbiota will aid in the development of treatments for diseases characterized by disturbances in the gut microbiome such as Clostridum difficile infection and metabolic diseases in at risk populations such as postmenopausal women.

Available for download on Wednesday, April 20, 2022

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