Down-regulation of hepatic stearoyl-CoA desaturase 1 expression by angiotensin II receptor blocker in the obese fa/fa Zucker rat: possible role in amelioration of insulin resistance and hepatic steatosis.
BACKGROUND
It has been reported that angiotensin II type 1 receptor blocker (ARB) can ameliorate hepatic steatosis and insulin resistance. Stearoyl-CoA desaturase 1 (SCD-1), which catalyzes the cellular synthesis of monounsaturated fatty acids, affects lipid metabolism. In this study, we investigated whether SCD-1 gene expression is affected by ARB treatment.


METHODS
Obese fa/fa Zucker rats fed a high-fat diet were treated with a potent ARB and olmesartan, and the resulting changes in the components of serum and liver were studied. Gene expression of hepatic SCD-1 was assayed using real-time PCR.


RESULTS
The serum glucose and insulin levels and hepatic TG content of the obese Zucker rats fed a high-fat diet were reduced after olmesartan administration, while the serum adiponectin level was increased. Real-time PCR revealed an increase of SCD-1 gene expression in the liver of these rats, followed by a reduction after olmesartan administration. The ratio of stearic acid (C18:0) to oleic acid (C18:1) in the liver was increased by olmesartan, indicating a reduction in the in vivo activity of SCD-1.


CONCLUSIONS
ARB ameliorates hepatic steatosis and insulin resistance in obese fa/fa Zucker rats fed a high-fat diet. Gene expression of SCD-1 is decreased by olmesartan, suggesting that the beneficial effect is due partly to suppression of the key enzyme for hepatic lipid metabolism by ARB.
Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Junji
J
Yokozawa
Takashi
T
Sasaki
Kumiko
K
Ohwada
Yayoi
Y
Sasaki
Jun-Itsu
JI
Ito
Takafumi
T
Saito
Sumio
S
Kawata
D052242:Adiponectin / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000503:physiopathology* / Q000517:prevention & control; D015870:Gene Expression / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011924:Rats, Zucker; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology*; D014280:Triglycerides / Q000032:analysis
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D005230:Fatty Acids, Nonesterified; D007093:Imidazoles; D013777:Tetrazoles; D014280:Triglycerides; C437965:olmesartan; D013230:Stearoyl-CoA Desaturase