Sex-specific differences in hepatic steatosis in obese spontaneously hypertensive (SHROB) rats

Qingming Dong, Michael S. Kuefner, Xiong Deng, Dave Bridges, Edwards Park, Marshall Elam, Rajendra Raghow

Research output: Contribution to journalArticle

Abstract

Background: Patients with metabolic syndrome, who are characterized by co-existence of insulin resistance, hypertension, hyperlipidemia, and obesity, are also prone to develop non-alcoholic fatty liver disease (NAFLD). Although the prevalence and severity of NAFLD is significantly greater in men than women, the mechanisms by which gender modulates the pathogenesis of hepatic steatosis are poorly defined. The obese spontaneously hypertensive (SHROB) rats represent an attractive model of metabolic syndrome without overt type 2 diabetes. Although pathological manifestation caused by the absence of a functional leptin receptor has been extensively studied in SHROB rats, it is unknown whether these animals elicited sex-specific differences in the development of hepatic steatosis. Methods: We compared hepatic pathology in male and female SHROB rats. Additionally, we examined key biochemical and molecular parameters of signaling pathways linked with hyperinsulinemia and hyperlipidemia. Finally, using methods of quantitative polymerase chain reaction (qPCR) and western blot analysis, we quantified expression of 45 genes related to lipid biosynthesis and metabolism in the livers of male and female SHROB rats. Results: We show that all SHROB rats developed hepatic steatosis that was accompanied by enhanced expression of SREBP1, SREBP2, ACC1, and FASN proteins. The livers of male rats also elicited higher induction of Pparg, Ppara, Slc2a4, Atox1, Skp1, Angptl3, and Pnpla3 mRNAs. In contrast, the livers of female SHROB rats elicited constitutively higher levels of phosphorylated JNK and AMPK and enhanced expression of Cd36. Conclusion: Based on these data, we conclude that the severity of hepatic steatosis in male and female SHROB rats was mainly driven by increased de novo lipogenesis. Moreover, male and female SHROB rats also elicited differential severity of hepatic steatosis that was coupled with sex-specific differences in fatty acid transport and esterification.

Original languageEnglish (US)
Article number40
JournalBiology of Sex Differences
Volume9
Issue number1
DOIs
StatePublished - Sep 10 2018

Fingerprint

Inbred SHR Rats
Sex Characteristics
Disease
Liver
hypertension
coexistence
induction
pathology
chronic illness
animal
gender
Hyperlipidemias
Leptin Receptors
Lipogenesis
AMP-Activated Protein Kinases
Esterification
Hyperinsulinism
Lipid Metabolism
Type 2 Diabetes Mellitus
Insulin Resistance

All Science Journal Classification (ASJC) codes

  • Gender Studies
  • Endocrinology

Cite this

Sex-specific differences in hepatic steatosis in obese spontaneously hypertensive (SHROB) rats. / Dong, Qingming; Kuefner, Michael S.; Deng, Xiong; Bridges, Dave; Park, Edwards; Elam, Marshall; Raghow, Rajendra.

In: Biology of Sex Differences, Vol. 9, No. 1, 40, 10.09.2018.

Research output: Contribution to journalArticle

@article{273f5510258f4ed69e3bb9cd0febb575,
title = "Sex-specific differences in hepatic steatosis in obese spontaneously hypertensive (SHROB) rats",
abstract = "Background: Patients with metabolic syndrome, who are characterized by co-existence of insulin resistance, hypertension, hyperlipidemia, and obesity, are also prone to develop non-alcoholic fatty liver disease (NAFLD). Although the prevalence and severity of NAFLD is significantly greater in men than women, the mechanisms by which gender modulates the pathogenesis of hepatic steatosis are poorly defined. The obese spontaneously hypertensive (SHROB) rats represent an attractive model of metabolic syndrome without overt type 2 diabetes. Although pathological manifestation caused by the absence of a functional leptin receptor has been extensively studied in SHROB rats, it is unknown whether these animals elicited sex-specific differences in the development of hepatic steatosis. Methods: We compared hepatic pathology in male and female SHROB rats. Additionally, we examined key biochemical and molecular parameters of signaling pathways linked with hyperinsulinemia and hyperlipidemia. Finally, using methods of quantitative polymerase chain reaction (qPCR) and western blot analysis, we quantified expression of 45 genes related to lipid biosynthesis and metabolism in the livers of male and female SHROB rats. Results: We show that all SHROB rats developed hepatic steatosis that was accompanied by enhanced expression of SREBP1, SREBP2, ACC1, and FASN proteins. The livers of male rats also elicited higher induction of Pparg, Ppara, Slc2a4, Atox1, Skp1, Angptl3, and Pnpla3 mRNAs. In contrast, the livers of female SHROB rats elicited constitutively higher levels of phosphorylated JNK and AMPK and enhanced expression of Cd36. Conclusion: Based on these data, we conclude that the severity of hepatic steatosis in male and female SHROB rats was mainly driven by increased de novo lipogenesis. Moreover, male and female SHROB rats also elicited differential severity of hepatic steatosis that was coupled with sex-specific differences in fatty acid transport and esterification.",
author = "Qingming Dong and Kuefner, {Michael S.} and Xiong Deng and Dave Bridges and Edwards Park and Marshall Elam and Rajendra Raghow",
year = "2018",
month = "9",
day = "10",
doi = "10.1186/s13293-018-0202-x",
language = "English (US)",
volume = "9",
journal = "Biology of Sex Differences",
issn = "2042-6410",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Sex-specific differences in hepatic steatosis in obese spontaneously hypertensive (SHROB) rats

AU - Dong, Qingming

AU - Kuefner, Michael S.

AU - Deng, Xiong

AU - Bridges, Dave

AU - Park, Edwards

AU - Elam, Marshall

AU - Raghow, Rajendra

PY - 2018/9/10

Y1 - 2018/9/10

N2 - Background: Patients with metabolic syndrome, who are characterized by co-existence of insulin resistance, hypertension, hyperlipidemia, and obesity, are also prone to develop non-alcoholic fatty liver disease (NAFLD). Although the prevalence and severity of NAFLD is significantly greater in men than women, the mechanisms by which gender modulates the pathogenesis of hepatic steatosis are poorly defined. The obese spontaneously hypertensive (SHROB) rats represent an attractive model of metabolic syndrome without overt type 2 diabetes. Although pathological manifestation caused by the absence of a functional leptin receptor has been extensively studied in SHROB rats, it is unknown whether these animals elicited sex-specific differences in the development of hepatic steatosis. Methods: We compared hepatic pathology in male and female SHROB rats. Additionally, we examined key biochemical and molecular parameters of signaling pathways linked with hyperinsulinemia and hyperlipidemia. Finally, using methods of quantitative polymerase chain reaction (qPCR) and western blot analysis, we quantified expression of 45 genes related to lipid biosynthesis and metabolism in the livers of male and female SHROB rats. Results: We show that all SHROB rats developed hepatic steatosis that was accompanied by enhanced expression of SREBP1, SREBP2, ACC1, and FASN proteins. The livers of male rats also elicited higher induction of Pparg, Ppara, Slc2a4, Atox1, Skp1, Angptl3, and Pnpla3 mRNAs. In contrast, the livers of female SHROB rats elicited constitutively higher levels of phosphorylated JNK and AMPK and enhanced expression of Cd36. Conclusion: Based on these data, we conclude that the severity of hepatic steatosis in male and female SHROB rats was mainly driven by increased de novo lipogenesis. Moreover, male and female SHROB rats also elicited differential severity of hepatic steatosis that was coupled with sex-specific differences in fatty acid transport and esterification.

AB - Background: Patients with metabolic syndrome, who are characterized by co-existence of insulin resistance, hypertension, hyperlipidemia, and obesity, are also prone to develop non-alcoholic fatty liver disease (NAFLD). Although the prevalence and severity of NAFLD is significantly greater in men than women, the mechanisms by which gender modulates the pathogenesis of hepatic steatosis are poorly defined. The obese spontaneously hypertensive (SHROB) rats represent an attractive model of metabolic syndrome without overt type 2 diabetes. Although pathological manifestation caused by the absence of a functional leptin receptor has been extensively studied in SHROB rats, it is unknown whether these animals elicited sex-specific differences in the development of hepatic steatosis. Methods: We compared hepatic pathology in male and female SHROB rats. Additionally, we examined key biochemical and molecular parameters of signaling pathways linked with hyperinsulinemia and hyperlipidemia. Finally, using methods of quantitative polymerase chain reaction (qPCR) and western blot analysis, we quantified expression of 45 genes related to lipid biosynthesis and metabolism in the livers of male and female SHROB rats. Results: We show that all SHROB rats developed hepatic steatosis that was accompanied by enhanced expression of SREBP1, SREBP2, ACC1, and FASN proteins. The livers of male rats also elicited higher induction of Pparg, Ppara, Slc2a4, Atox1, Skp1, Angptl3, and Pnpla3 mRNAs. In contrast, the livers of female SHROB rats elicited constitutively higher levels of phosphorylated JNK and AMPK and enhanced expression of Cd36. Conclusion: Based on these data, we conclude that the severity of hepatic steatosis in male and female SHROB rats was mainly driven by increased de novo lipogenesis. Moreover, male and female SHROB rats also elicited differential severity of hepatic steatosis that was coupled with sex-specific differences in fatty acid transport and esterification.

UR - http://www.scopus.com/inward/record.url?scp=85053144830&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053144830&partnerID=8YFLogxK

U2 - 10.1186/s13293-018-0202-x

DO - 10.1186/s13293-018-0202-x

M3 - Article

VL - 9

JO - Biology of Sex Differences

JF - Biology of Sex Differences

SN - 2042-6410

IS - 1

M1 - 40

ER -