[The effects of renin-angiotensin system blockade on the liver steatosis in rats on long-term high-fat diet].
OBJECTIVE
To observe the relationship between liver steatosis in rats with long-term high-caloric and high-fat diet and the expression of angiotensinogen (AGT), uncoupling protein 2 (UCP-2) and transforming growth factor beta1 (TGFbeta1). Then angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) drugs were given to investigate whether rennin-angiotensin system (RAS) blockade can mitigate the liver steatosis and to probe its mechanisms.


METHODS
Forty male Wistar rats were divided into normal control group (NC group, n = 10), high-calorie and high-fat fed group (HF group, n = 10), ARB treated group (AR group, n = 10) and ACEI treated group (AE group, n = 10). Rats were fed with high-calorie and high-fat diet and given RAS inhibitor drugs (valsartan 40 mg/kg to the AR group and perindopril 4 mg/kg to the AE group) for eight weeks. Serum TG, free fatty acids (FFAs) lever and the fat content in liver were then measured with biochemical tests; insulin resistance was evaluated with euglycemic hyperinsulinemia clamp technique, the expression of UCP-2 and TGFbeta1 in liver tissue were examined with immunohistochemical staining and AGT mRNA, UCP-2 mRNA and TGFbeta1 mRNA were tested with RT-PCR.


RESULTS
With the administration of RAS inhibitor drugs, following changes were observed. The levels of TG and FFAs and the fat content in liver decreased (P < 0.01 or P < 0.05), insulin resistance in high-fat fed rats was improved (P < 0.05), liver steatosis, inflammation and fibrosis were mitigated. The levels of UCP-2 decreased by 36.5% (P < 0.05) in AE group and 42.5% (P < 0.05) in AR group and TGFbeta1 decreased by 37% (P < 0.05) in AE group and 41.6% (P < 0.05) in AR group as compared with the HF group with immunohistochemical staining. The expression of AGTmRNA decreased by 14.9% (P < 0.05) in AE group and 21% (P < 0 .05) in AR group, UCP-2 mRNA decreased by 9% (P < 0.05) in AE group and 11% (P < 0.05) in AR group and TGFbeta1 mRNA decreased by 17% (P < 0.05) in AE group and 19% (P < 0.05) in AR group as compared with the HF group with RT-PCR.


CONCLUSIONS
RAS blockade could improve insulin resistance, mitigate the liver injury of long term high-fat fed rats and have a protective effect on liver. The mechanism may be associated with the effects of improved insulin resistance, the interaction within RAS and the down-regulation of UCP-2 and TGFbeta1 in liver tissue.
Chen
Ying-Hua
YH
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Yuan
Li
L
Chen
Yuan-Yuan
YY
Qi
Cui-Juan
CJ
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000502:physiology; D007473:Ion Channels / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics; D000071246:Uncoupling Protein 2; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004041:Dietary Fats; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D000068756:Valsartan; D014633:Valine; D020913:Perindopril