Abstract
Liver regeneration is a perfectly calibrated mechanism crucial to increase mass recovery of small size grafts from living donor liver transplantation, as well as in other surgical procedures including hepatic resections and liver transplantation from cadaveric donors. Regeneration involves multiple events and pathways in which several adipokines contribute to their orchestration and drive hepatocytes to proliferate. In addition, ischemia-reperfusion injury is a critical factor in hepatic resection and liver transplantation associated with liver failure or graft dysfunction post-surgery. This review aims to summarize the existing knowledge in the role of adipokines in surgical procedures requiring both liver regeneration and vascular occlusion, which increases ischemia-reperfusion injury and regenerative failure. We expose and discuss results in small-for-size liver transplantation and hepatic resections from animal studies focused on the modulation of the main adipokines associated with liver diseases and/or regeneration published in the last five years and analyze future perspectives and their applicability as potential targets to decrease ischemia-reperfusion injury and improve regeneration highlighting marginal states such as steatosis. In our view, adipokines means a promising approach to translate to the bedside to improve the recovery of patients subjected to partial hepatectomy and to increase the availability of organs for transplantation.
Highlights
The ability of the liver to regenerate even when 70% of the organ tissue has been removed [1] together with the shortage of liver grafts from deceased donors have led to an increased interest in living donor liver transplantation (LDLT), where healthy donors undergo anatomical hepatectomy [2], and split liver transplantation from cadaveric donors to be used in two recipients [3]
The presence of fatty infiltration is associated with poor outcome after surgery and pre-existing steatosis is related with impairment of liver regeneration following partial hepatectomy (PH) [4]
Xu et al reported that hepatocyte-derived LCN2 after treatment with interleukin 6 (IL-6) promoted liver regeneration after PH. These discrepancies might be explained because the different methods to quantify liver regeneration [23]. It is worth noting the potential of this protein, a cytokine firstly used as a biomarker for renal injury and inflammation that later was described as the major positive acute-phase protein in rat during acute-phase reaction by Sultan et al they found that the liver and not the kidney is the main source of serum LCN2 in the case of tissue damage [84]
Summary
The ability of the liver to regenerate even when 70% of the organ tissue has been removed [1] together with the shortage of liver grafts from deceased donors have led to an increased interest in living donor liver transplantation (LDLT), where healthy donors undergo anatomical hepatectomy [2], and split liver transplantation from cadaveric donors to be used in two recipients [3]. Mediates inflammatory responses, serving as a chemo attractant to induce influx of macrophages and natural killer cells [12] Regulator of both the immune and the nervous system as well in liver regeneration [13]. It has been related with angiogenesis and pro-inflammatory cytokines. Regulates lipid metabolism and fatty acid oxidation [27] It is implied in the development of liver cirrhosis, portal hypertension, angiogenesis and apoptosis [28]. The soluble form induces mitogenic and regenerative activities [3] Proliferation, morphogenesis and anti-apoptosis [31] Both prenatal and postnatal development, including cell growth, differentiation, migration, and survival [32]. IL-6: interleukin 6; TNF-α: tumor necrosis factor alpha; LCN: lipocalin; RBP4: retinol-binding protein 4; HB-EGF: heparin-binding epidermal growth factor; VEGF: vascular endothelial growth factor; TGF-β: tumor growth factor-β; PAI-1: phosphoribosylanthranilate isomerase 1; DKL-1: delta like-1 homologue; IGF: insulin growth factor; NGF: nerve growth factor; HGF: hepatocyte growth factor
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