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.
Yokozawa
Junji
J
Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Sasaki
Takashi
T
Ohwada
Kumiko
K
Sasaki
Yayoi
Y
Ito
Jun-Itsu
JI
Saito
Takafumi
T
Kawata
Sumio
S
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