Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats

详细信息    查看全文

• 作者：Patrí ; cia C. Lopes^a ; Amelia Fuhrmann^a ; José ; Sereno^b ; ^c ; Daniel O. Espinoza^a ; Maria Joã ; o Pereira^a ; ^d ; Jan W. Eriksson^d ; Flá ; vio Reis^b ; Eugenia Carvalho^a ; ^e ; ^{ecarvalh@cnc.uc.pt" class="auth_mail}
• 关键词：ACC ; Acetyl-CoA carboxylase ; ATGL ; Adipose triacylglycerol lipase ; CD36 ; Fatty acid translocase ; CsA ; Cyclosporine A ; CHREBP ; Carbohydrate response element-binding protein ; DGAT1 ; Diglyceride acyltransferase 1 ; FAS ; Fatty acid synthase ; FFA ; Free Fatty Acid ; HSL ; Hormone-sensitive lipase ; IA ; Immunosuppressive agent ; IL-6 ; Interleukin-6 ; LDL ; Low-density lipoprotein ; LPL ; Lipoprotein lipase ; mTOR ; Mammalian target of rapamycin ; NEFA ; non-esterified fatty acid ; NODAT ; New onset diabetes after tra
• 刊名：Metabolism
• 出版年：May, 2014
• 年：2014
• 卷：63
• 期：5
• 页码：702-715
• 全文大小：1828 K

文摘

Objective

Cyclosporine A (CsA) and sirolimus (SRL) are immunosuppressive agents (IA) associated with new onset diabetes after transplantation and dyslipidemia. We aim to evaluate the molecular effects of CsA (5 mg/kg/day) and SRL (1 mg/kg/day) treatment for 3 and 9 weeks on lipid metabolism, in Wistar rats.

Materials/Methods

Lipolysis was evaluated in isolated adipocytes, while triglycerides (TG) and non-esterified fatty acid (NEFA) were measured in serum. Gene and protein expression involved in lipid metabolism was assessed in adipose tissue and liver.

Results

CsA and SRL treatments of rats for 3 and 9 weeks increased isoproterenol-stimulated lipolysis by 5-9 fold and 4-6 fold in isolated adipocytes, respectively. While CsA increased adipocyte weight and diameter, as well as NEFA and TG levels in circulation after 9 weeks, SRL treatment caused ectopic deposition of TG in the liver after 3 weeks. Moreover, ACC1 and FAS protein expression was increased after 3 weeks (> 100%, p < 0.01), while HSL was increased after 9 weeks of CsA treatment. On the other hand, SRL decreased the expression of lipogenic genes, including ACC1 (50%, p < 0.05), lipin1 (25%, p < 0.05), PPAR-纬 (42%, p < 0.05) and SCD1 (80%, p < 0.001) in adipose tissue, after 3 weeks of treatment.

Conclusion

The effects of both IAs on expression of lipolytic and lipogenic genes suggest that these agents influence lipid metabolism, thus contributing to the dyslipidemia observed during immunosuppressive therapy.