The effects of glucose and lipids in steatotic and non‐steatotic livers in conditions of partial hepatectomy under ischaemia‐reperfusion

Mendes‐Braz, Mariana; Elias-Miró, M.; Kleuser, Burkhard; Fayyaz, Susann; Jiménez‐Castro, Mónica B.; Massip-Salcedo, Marta; Gracia‐Sancho, Jordi; Ramalho, Fernando Silva; Rodés, Juan; Peralta, Carmen

doi:10.1111/liv.12348

Cited by 19 publications

(40 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Procedural subsets were as follows: ( i ) dissection of hepatic hilar vessels (sham); ( ii ) PH (70%); ( iii ) PH (70%) + I/R (60‐min. ischaemic period), standard throughout; ( iv ) PH + I/R after initial lipectomy of retroperitoneal and epididymal white adipose tissue (PH + I/R + LPT) ; ( v ) PH + I/R + cortisol [5 mg/kg, intraperitoneal (IP)] 10 min. preoperatively ; ( vi ) PH + I/R + ACh [500 μg/kg, intravenous (IV)] 10 min.…”

Section: Methodsmentioning

confidence: 99%

The impact of cortisol in steatotic and non‐steatotic liver surgery

Cornide‐Petronio

Bujaldon

Mendes‐Braz

et al. 2017

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

The intent of this study was to examine the effects of regulating cortisol levels on damage and regeneration in livers with and without steatosis subjected to partial hepatectomy under ischaemia-reperfusion. Ultimately, we found that lean animals undergoing liver resection displayed no changes in cortisol, whereas cortisol levels in plasma, liver and adipose tissue were elevated in obese animals undergoing such surgery. Such elevations were attributed to enzymatic upregulation, ensuring cortisol production, and downregulation of enzymes controlling cortisol clearance. In the absence of steatosis, exogenous cortisol administration boosted circulating cortisol, while inducing clearance of hepatic cortisol, thus maintaining low cortisol levels and preventing related hepatocellular harm. In the presence of steatosis, cortisol administration was marked by a substantial rise in intrahepatic availability, thereby exacerbating tissue damage and regenerative failure. The injurious effects of cortisol were linked to high hepatic acethylcholine levels. Upon administering an a7 nicotinic acethylcholine receptor antagonist, no changes in terms of tissue damage or regenerative lapse were apparent in steatotic livers. However, exposure to an M3 muscarinic acetylcholine receptor antagonist protected livers against damage, enhancing parenchymal regeneration and survival rate. These outcomes for the first time provide new mechanistic insight into surgically altered steatotic livers, underscoring the compelling therapeutic potential of cortisol-acetylcholine-M3 muscarinic receptors.

show abstract

Section: Methodsmentioning

confidence: 99%

The impact of cortisol in steatotic and non‐steatotic liver surgery

Cornide‐Petronio

Bujaldon

Mendes‐Braz

et al. 2017

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, steatotic livers show differences in the regenerative response and less tolerance to damage in comparison with nonsteatotic livers . Data from preclinical studies indicate that impaired regeneration in steatotic livers was associated with interruption of the normal IL6 signaling pathway and failure of signaling at the level of the G 1 /S phase transition in the cell cycle during hepatocyte proliferation .…”

Section: Mechanisms Involved In Iri In Steatotic Ltmentioning

confidence: 99%

“…On the other hand, steatotic livers show differences in the regenerative response and less tolerance to damage in comparison with nonsteatotic livers. (57,68,69) Data from preclinical studies indicate that impaired regeneration in steatotic livers was associated with interruption of the normal IL6 signaling pathway and failure of signaling at the level of the G 1 /S phase transition in the cell cycle during hepatocyte proliferation. (70,71) This arrest has been proposed to be due to a combination of factors, such as the inhibition of induction of the cyclin D1 gene and mitogen-activated protein kinase (MAPK) in the G 1 phase of cell cycle.…”

Section: Effects Of Steatosis and Bd On Regeneration In Ltmentioning

confidence: 99%

“…Many of the previously mentioned studies (13 of 23) were performed in rat models with moderate steatotic livers. (53,57,62,63,65,66,76,(78)(79)(80)84,86,87) Of these studies,11 used fatty livers from Zucker rats (53,57,62,63,65,66,68,77,78,(87)(88)(89) ; 5 used a methionine-choline deficient diet (53,68,82,83,89) and 5 a HFD, (64,(79)(80)(81)85,88) both models of steatohepatitis. Finally, in 2 studies steatohepatitis was induced by alcohol.…”

Section: Therapeutic Strategies Applied In Steatotic Livers For Transmentioning

confidence: 99%

See 1 more Smart Citation

Use of Steatotic Grafts in Liver Transplantation: Current Status

et al. 2019

Self Cite

View full text Add to dashboard Cite

In the field of liver transplantation, the demand for adequate allografts greatly exceeds the supply. Therefore, expanding the donor pool to match the growing demand is mandatory. The present review summarizes current knowledge of the pathophysiology of ischemia/reperfusion injury in steatotic grafts, together with recent pharmacological approaches aimed at maximizing the utilization of these livers for transplantation. We also describe the preclinical models currently available to understand the molecular mechanisms controlling graft viability in this specific type of donor, critically discussing the heterogeneity in animal models, surgical methodology, and therapeutic interventions. This lack of common approaches and interventions makes it difficult to establish the pathways involved and the relevance of isolated discoveries, as well as their transferability to clinical practice. Finally, we discuss how new therapeutic strategies developed from experimental studies are promising but that further studies are warranted to translate them to the bedside.

show abstract

“…Interestingly, adipose tissue does not seem to be an energy source for the steatotic liver; indeed ATP levels were maintained after lipectomy, but adipose tissue is a source of different adipocytokines, which are essential signals for liver regeneration [31]. Considering that, in clinical practice, PH is usually accompanied by I/R, a recent study has evaluated the contribution of adipose tissue to liver injury and regeneration observed in these surgical conditions.…”

Section: Adipose Tissue and Adipocytokinesmentioning

confidence: 99%

Molecular pathways in protecting the liver from ischaemia/reperfusion injury: a 2015 update

2015

Self Cite

View full text Add to dashboard Cite

Ischaemia/reperfusion injury is an important cause of liver damage during surgical procedures such as hepatic resection and liver transplantation, and represents the main cause of graft dysfunction post-transplantation. Molecular processes occurring during hepatic ischaemia/reperfusion are diverse, and continuously include new and complex mechanisms. The present review aims to summarize the newest concepts and hypotheses regarding the pathophysiology of liver ischaemia/reperfusion, making clear distinction between situations of cold and warm ischaemia. Moreover, the most updated therapeutic strategies including pharmacological, genetic and surgical interventions, as well as some of the scientific controversies in the field are described.

show abstract

The effects of glucose and lipids in steatotic and non‐steatotic livers in conditions of partial hepatectomy under ischaemia‐reperfusion

Abstract: Lipid treatment in non-steatotic livers provides the same protection as that afforded by glucose in conditions of PH under I/R, whereas the treatment with lipids is preferable to reduce the injurious effects of liver surgery in the presence of steatosis.

Cited by 19 publications

References 77 publications

The impact of cortisol in steatotic and non‐steatotic liver surgery

The impact of cortisol in steatotic and non‐steatotic liver surgery

Use of Steatotic Grafts in Liver Transplantation: Current Status

Molecular pathways in protecting the liver from ischaemia/reperfusion injury: a 2015 update

Contact Info

Product

Resources

About