PPARα is down-regulated following liver transplantation in mice

Nakagawa, Kan; Tanaka, Naoki; Sugioka, Atsushi; Miyagawa, Shinichi; Gonzalez, Frank J.; Aoyama, Toshifumi

doi:10.1016/j.jhep.2011.08.021

Cited by 11 publications

(4 citation statements)

References 48 publications

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“…In addition, hepatic PPARα expression is reported to be associated with ischemia-reperfusion injury. 20 Therefore, strategies based on hepatic PPARα regulation have the potential to improve the prognosis of patients undergoing LT 21 and to expand the organ donor pool, which is in great shortage.…”

Section: Discussionmentioning

confidence: 99%

Donor PPARα Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients

Ling

Xu²,

Wang³

et al. 2015

Medicine

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Section: Discussionmentioning

confidence: 99%

Donor PPARα Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients

Ling

Xu²,

Wang³

et al. 2015

Medicine

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“…The role of PPAR α has been clarified in several liver diseases. For instance, PPAR α is downregulated in alcoholic liver disease [ 11 , 36 ] as well as after liver transplantation[ 37 ]. Persistent activation of PPAR α ameliorates hepatic steatosis and inflammation in mice but may also induce hepatocarcinogenesis [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice

et al. 2012

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Sulfatides are one of the major sphingoglycolipids in mammalian serum and are synthesized and secreted mainly from the liver as a component of lipoproteins. Recent studies revealed a protective role for serum sulfatides against arteriosclerosis and hypercoagulation. Although peroxisome proliferator-activated receptor (PPAR) α has important functions in hepatic lipoprotein metabolism, its association with sulfatides has not been investigated. In this study, sulfatide levels and the expression of enzymes related to sulfatide metabolism were examined using wild-type (+/+), Ppara-heterozygous (+/−), and Ppara-null (−/−) mice given a control diet or one containing 0.1% fenofibrate, a clinically used hypolipidemic drug and PPARα activator. Fenofibrate treatment increased serum and hepatic sulfatides in Ppara (+/+) and (+/−) mice through a marked induction of hepatic cerebroside sulfotransferase (CST), a key enzyme in sulfatide synthesis, in a PPARα-dependent manner. Furthermore, increases in CST mRNA levels were correlated with mRNA elevations of several known PPARα target genes, and such changes were not observed for other sulfatide-metabolism enzymes in the liver. These results suggest that PPARα activation enhances hepatic sulfatide synthesis via CST induction and implicate CST as a novel PPARα target gene.

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“…Kurian et al further identified pathways (PPARα and NF-κB) and targets (i.e., IL-1, CXCL1, TIPARP, TRAF6, and TNFRSF1B) that contribute to the onset of EAD by global gene expression profile analysis ( 15 ). Further research has revealed that PPARα is downregulated after LT, which might be an adaptive response to oxidative stress and hepatocellular damage during LT ( 16 ). Moreover, microRNAs and circular RNAs, such as miRNA-122, circFOXN2, and circNEXTIN3, that are expressed in the liver have been found to be potential early predictors of the onset of EAD ( 6 , 7 ).…”

Section: Discussionmentioning

confidence: 99%

Combination of Early Allograft Dysfunction and Protein Expression Patterns Predicts Outcome of Liver Transplantation From Donation After Cardiac Death

et al. 2021

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Early allograft dysfunction (EAD) after liver transplantation (LT) accompanies poor prognosis. This study aims to explore the relationship between pretransplant intrahepatic proteins and the incidence of EAD, and the value of combined EAD and protein profiles for predicting recipient and graft survival prognosis. Liver biopsy specimens of 105 pretransplant grafts used for LT were collected and used for immunohistochemistry analysis of 5 proteins. And matched clinical data of donor, recipient, transplantation, and prognosis were analyzed. The incidence of EAD was 41.9% (44/105) in this cohort. Macrovesicular steatosis (P = 0.016), donor body mass index (P = 0.013), recipients' pretransplant serum creatinine (P = 0.036), and intrahepatic expression of heme oxygenase 1 (HO1) (P = 0.015) and tumor necrosis factor α (TNF-α) (P = 0.039) were independent predictors of EAD. Inferior graft and recipient prognosis were observed in patients who experienced EAD (P = 0.028 and 0.031) or received grafts with higher expression of sirtuin 1 (P = 0.005 and 0.013). The graft and recipient survival were worst in patients with both EAD and high expression of sirtuin 1 (P = 0.001 and 0.004). In conclusion, pretransplant intrahepatic expression of HO1 and TNF-α are associated with the incidence of EAD. The combination of EAD and EAD-unrelated proteins showed superiority in distinguishing recipients with worse prognosis.

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PPARα is down-regulated following liver transplantation in mice

Abstract: Down-regulation of PPARα seemed to be an adaptive response to metabolic alterations following liver transplantation. These results provide novel information to the understanding of the pathogenesis of early post-transplant events.

Cited by 11 publications

References 48 publications

Donor PPARα Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients

Donor PPARα Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients

Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice

Combination of Early Allograft Dysfunction and Protein Expression Patterns Predicts Outcome of Liver Transplantation From Donation After Cardiac Death

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