- 作者：Maria Elias-Mir贸 ; Mariana Mendes-Braz ; Ruben Cereijo ; Francesc Villarroya ; M贸nica B. Jim茅nez-Castro ; Jordi Gracia-Sancho ; Sergi Guix茅-Muntet ; Marta Massip-Salcedo ; Joan Carles Domingo ; Raquel Bermudo ; Juan Rod茅s ; Carmen Peralta
- 关键词：PH ; partial hepatectomy ; I/R ; ischemia-reperfusion ; Nampt ; nicotinamide phosphoribosyltransferase ; NAD ; nicotinamide adenine dinucleotide ; TNF ; tumor necrosis factor ; IL ; interleukin ; Ob ; obese ; Ln ; lean ; BrdU ; bromo-deoxyuridine ; AST ; aspartate aminotransferase ; ALT ; alanine aminotransferase ; HGF ; hepatocyte growth factor ; TGF ; transforming growth factor ; MPO ; myeloperoxidase ; MDA ; malondialdehyde ; LDL ; Low-density lipoprotein ; VLDL ; very-low-density lipoprotein ; HDL ; high-density lipoprotein
- 刊名：Journal of Hepatology
- 出版年：January, 2014
- 年：2014
- 卷：60
- 期：1
- 页码：87-95
- 全文大小：1242 K
Background & Aims
This study examined whether the regulation of resistin and visfatin could reduce damage and improve regeneration in both steatotic and non-steatotic livers undergoing partial hepatectomy under ischemia-reperfusion, a procedure commonly applied in clinical practice to reduce bleeding.Methods
Resistin and visfatin were pharmacologically modulated in lean and obese animals undergoing partial hepatectomy under ischemia-reperfusion.
Results
No evident role for these adipocytokines was observed in non-steatotic livers. However, obese animals undergoing liver surgery showed increased resistin in liver and plasma, without changes in adipose tissue, together with visfatin downregulation in liver and increment in plasma and adipose tissue. Endogenous resistin maintains low levels of visfatin in the liver by blocking its hepatic uptake from the circulation, thus regulating the visfatin detrimental effects on hepatic damage and regenerative failure. Indeed, the administration of anti-resistin antibodies increased hepatic accumulation of adipocyte-derived visfatin, exacerbating damage and regenerative failure. Interestingly, treatment with anti-visfatin antibodies protected steatotic livers, and similar results were obtained with the concomitant inhibition of resistin and visfatin. Thus, when visfatin was inhibited, the injurious effects of anti-resistin antibodies disappeared. Herein we show that upregulation of visfatin increased NAD levels in the remnant steatotic liver, whereas visfatin inhibition decreased them. These later observations suggest that visfatin may favour synthesis of NAD instead of DNA and induces alterations in amino acid metabolism-urea cycle and NO production, overall negatively affecting liver viability.
Conclusions
Our results indicate the clinical potential of visfatin blocking-based therapies in steatotic livers undergoing partial hepatectomy with ischemia-reperfusion.