Premium
Analysis of Gene Expression in a Female Rat Model of Diet‐induced Non‐alcoholic Fatty Liver Disease Using RNA‐sequencing
Author(s) -
Bowman John James,
Lee Jennifer Karin,
Perets Ron A,
Knabe Melina L,
Guider Jamie W,
Phillips Scott,
Sarwadnya Uma D,
Blythe Sarah N,
Toporikova Natalia,
Whitworth Gregg B
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.944.6
Subject(s) - fatty liver , endocrinology , medicine , steatosis , estrogen , biology , gene expression , adipose tissue , gene , disease , biochemistry
We have established a diet‐induced model of non‐alcoholic fatty liver disease (NAFLD) in the adult female rat, which we have characterized through RNA‐seq, histology, and physiological measurements. Furthermore, we investigated whether peripheral estrogen signaling has affected this disease. All rats were ovariectomized, with basal levels of estrogen restored in half the animals by implantation of a slow release estradiol pellet. We observed a significant effect of both diet and estrogen on animal weight gain, with animals fed a high‐fat, high‐sugar diet without supplemental estrogen demonstrating a >2‐fold increase in weight gain compared to control diet animals that received estradiol pellets. Our high‐fat, high‐sugar animals demonstrate physiological and histological markers of NAFLD, including steatosis, inflammation, and an increase in connective tissue in the liver. Additionally, we measured percent body fat, liver weight, percent liver fat, and insulin, glucose, triglycerides, and cholesterol levels. Moreover, we used RNA purified from liver tissues to quantify global changes in gene expression between our experimental groups through RNA‐seq, with the goal of identifying genes that are differentially expressed in the NAFLD induced animals. In addition, the quantification of certain promising gene targets using RT‐qPCR serves as validation for RNA‐seq. Interestingly we see the greatest effect on gene expression through the interaction between diet and estrogen. We will be discussing the in‐depth, high resolution gene analysis done on the liver tissues as it relates to the induction of this disease. A few initial pathways and processes that are upregulated in our high‐fat animals include the inflammatory cytokines and genes involved in lipid metabolism. Support or Funding Information Howard Hughes Medical Institute Jeffress Trust Awards Program Interdisciplinary Research R.E. Lee Summer Research Scholars