Effects of ovariectomy on PPAR alpha, SREBP-1c, and SCD-1 gene expression in the rat liver.
OBJECTIVE
To investigate whether estrogen deficiency modifies the expression of important genes involved in hepatic lipid regulation, PPAR alpha, SREBP-1c, and SCD-1, in association with fat accumulation in the liver of ovariectomized rats.


METHODS
Thirty female Sprague-Dawley rats were divided into three groups: sham-operated (n = 12), ovariectomized (n = 12), and ovariectomized with 17beta-estradiol replacement (n = 6). All animals were killed 8 weeks after surgery. In addition to liver triacylglycerol determination, transcripts levels and protein content of peroxisome proliferator-activated receptor alpha, liver sterol regulatory element-binding protein 1c, and stearoyl coenzyme Adesaturase 1 were quantified by quantitative real-time polymerase chain reaction and Western blot, respectively.


RESULTS
As expected, liver triacylglycerol levels were higher (51%; 21.9 +/- 2.6 vs 14.5 +/- 1.2 mg/g; P < 0.01) in ovariectomized compared with sham-operated rats. Peroxisome proliferator-activated receptor alpha mRNA levels were 66% lower (P < 0.01), whereas sterol regulatory element-binding protein 1 and stearoyl coenzyme A desaturase 1 transcript levels were 80% and 41% higher (P < 0.05), respectively, after estrogen removal. Our data on gene expression obtained with quantitative real-time polymerase chain reaction for peroxisome proliferator-activated receptor alpha and sterol regulatory element-binding protein 1c were confirmed by Western blots. All the effects of ovariectomy were prevented by 17beta-estradiol replacement, indicating a role for estrogens in the prevention of hepatic fat accumulation.


CONCLUSIONS
Our results suggest that a reduction in lipid oxidation and an increase in lipogenesis are defective mechanisms leading to lipid accumulation in the liver of ovariectomized rats. We conclude that estrogen deficiency induced by ovariectomy changes the expression of genes that favor the development of a steatotic phenotype.
Paquette
Amélie
A
Département de Kinésiologie, Université de Montréal, Montréal, Québec, Canada. amelie.paquette@umontreal.ca
Wang
Donghao
D
Jankowski
Marek
M
Gutkowska
Jolanta
J
Lavoie
Jean-Marc
JM
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism*; D008593:Menopause / Q000378:metabolism; D010052:Ovariectomy; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism
D004967:Estrogens; D047493:PPAR alpha; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D004958:Estradiol; D013230:Stearoyl-CoA Desaturase