Maria Elias-Miró1, Mariana Mendes-Braz2, Ruben Cereijo3, Francesc Villarroya3, Mónica B Jiménez-Castro1, Jordi Gracia-Sancho4, Sergi Guixé-Muntet4, Marta Massip-Salcedo1, Joan Carles Domingo5, Raquel Bermudo6, Juan Rodés7, Carmen Peralta8. 1. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain. 2. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain; Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. 3. Departament de Bioquímica i Biología Molecular, i Institut de Biomedicina, Universitat de Barcelona, CIBER Fisopatologia de la Obesidad y Nutrición, Spain. 4. Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS, CIBEREHD, Barcelona, Spain. 5. Department of Biochemistry and Molecular Biology, University of Barcelona, Spain. 6. Tumour Bank, IDIBAPS, Barcelona, Spain. 7. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain; Liver Unit, Hospital Clínic, Barcelona, Spain. 8. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain. Electronic address: cperalta@clinic.ub.es.
Abstract
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.
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.
Authors: Marc Micó-Carnero; Araní Casillas-Ramírez; Alfredo Sánchez-González; Carlos Rojano-Alfonso; Carmen Peralta Journal: Biomedicines Date: 2022-04-23
Authors: María Eugenia Cornide-Petronio; Esther Bujaldon; Mariana Mendes-Braz; Cindy G Avalos de León; Mónica B Jiménez-Castro; Ana I Álvarez-Mercado; Jordi Gracia-Sancho; Juan Rodés; Carmen Peralta Journal: J Cell Mol Med Date: 2017-04-04 Impact factor: 5.310