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Iqbal et al. Vessel Plus 2019;3:40 Vessel Plus
DOI: 10.20517/2574-1209.2019.28

Original Article Open Access

Deletion of retinoic acid-related orphan receptor
gamma reduces body weight and hepatic lipids
in mice by modulating the expression of lipid
metabolism genes

Jahangir Iqbal , Zainab Jahangir , Divya Veluru , Abeer Al Otaibi , Sindiyan A. Mubarak , Badr Al Subie ,
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1
1
1
2
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Ahmad F. Alghanem , Ali Al Qarni , Ahmed Bakillah , Abbas Hawwari
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1,3
1 King Abdullah International Medical Research Center-Eastern Region, King Saud Bin Abdulaziz University for Health Sciences,
Ministry of National Guard-Health Affairs, Al Ahsa 31982, Saudi Arabia.
2 JP Stevens High School, North Edison, NJ 08820, USA.
3 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Correspondence to: Dr. Jahangir Iqbal and Dr. Abbas Hawwari, King Abdullah International Medical Research Center, King
Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City Hospital, Ministry of National Guard Health
Affairs, Mail Code 520, Al Ahsa 31982, Saudi Arabia. E-mail: iqbalja@ngha.med.sa; hawwariab@ngha.med.sa
How to cite this article: Iqbal J, Jahangir Z, Veluru D, Otaibi AA, Mubarak SA, Subie BA, Alghanem AF, Qarni AA, Bakillah
A, Hawwari A. Deletion of retinoic acid-related orphan receptor gamma reduces body weight and hepatic lipids in mice by
modulating the expression of lipid metabolism genes. Vessel Plus 2019;3:40. http://dx.doi.org/10.20517/2574-1209.2019.28
Received: 5 Dec 2019 First Decision: 9 Dec 2019 Revised: 9 Dec 2019 Accepted: 16 Dec 2019 Published: 26 Dec 2019

Science Editor: Mario F. L. Gaudino Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Aim: Retinoic acid-related orphan receptor γ (RORγ) functions as a ligand-dependent transcription factor and its loss has
been shown to affect the circadian expression of lipid metabolism genes. However, its effect on body weight gain and
hepatic lipids is not well understood. In this study, we investigated the impact of Rorγ gene deletion on changes in body
weight and hepatic lipids.

Methods: Body weight and lipids were analyzed in the plasma and liver. Expression of lipid metabolism genes in the liver
was evaluated in wild type and Rorγ knockout mice.

Results: We show that deletion of RORγ results in reduced body weight and fewer lipids in the liver. Analysis of gene
expression showed that deletion of Rorγ resulted in an overall lower expression of genes and transcription factors
involved in lipid biosynthesis. We observed a decrease in the gene expression of cholesterol biosynthesis, efflux, and
esterification but an increase in bile acid synthesis. There was a decrease in fatty acid and triglycerides biosynthesis
genes and an increase in the fatty acid uptake genes. The decrease in the expression of lipid biosynthesis genes was
accompanied by the decrease in the sterol response element binding protein (Srebp) genes. We observed an increase in

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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