Functional Relationships between Lipid Metabolism and Liver Regeneration

Abstract

The regenerative capacity of the liver is well known, and the mechanisms that regulate this process have been extensively studied using experimental model systems including surgical resection and hepatotoxin exposure. The response to primary mitogens has also been used to investigate the regulation of hepatocellular proliferation. Such analyses have identified many specific cytokines and growth factors, intracellular signaling events, and transcription factors that are regulated during and necessary for normal liver regeneration. Nevertheless, the nature and identities of the most proximal events that initiate hepatic regeneration as well as those distal signals that terminate this process remain unknown. Here, we review the data implicating acute alterations in lipid metabolism as important determinants of experimental liver regeneration and propose a novel metabolic model of regeneration based on these data. We also discuss the association between chronic hepatic steatosis and impaired regeneration in animal models and humans and consider important areas for future research.

Dynamic changes in the mouse hepatic lipidome following warm ischemia reperfusion injury

“…Specifically, we noted significant TG accumulation in non-steatotic liver following IRI. This is in line with previous findings of transient steatosis following IRI (11) and partial hepatectomy (30). Of note, we did not see a similar increase in TG in steatotic liver.…”

Dynamic changes in the mouse hepatic lipidome following warm ischemia reperfusion injury

“…Specifically, we noted significant TG accumulation in non-steatotic liver following IRI. This is in line with previous findings of transient steatosis following IRI (11) and partial hepatectomy (30). Of note, we did not see a similar increase in TG in steatotic liver.…”

Investigation of the hepatic development in the coculture of hiPSCs-derived LSECs and HLCs in a fluidic microenvironment

“…5(d) ]. Those results could be related to previously observed fatty liver patterns ( Lee et al , 2015 ) and are consistent with in vivo regenerative patterns in the liver ( Rudnick and Davidson, 2012 ). In the present work, higher expression of FADS3 was found in the proteomic dataset of coculture biochips.…”

Maternal Hepatocytes Heterogeneously and Dynamically Exhibit Developmental Phenotypes Partially via YAP1 during Pregnancy

“…This finding enabled us to gain some mechanistic insight into the regulation of pregnancydependent phenotypic plasticity in maternal hepatocytes. In addition, YAP1 has been reported to regulate lipid metabolism, and activation of YAP1 in hepatocytes causes fatty liver (47)(48)(49)(50). In this study, we observed that the absence of YAP1 in maternal hepatocytes decreased cholesterol concentrations in the maternal circulation, consistent with these studies.…”

Dynamic changes in the mouse hepatic lipidome following warm ischemia reperfusion injury

“…Specifically, we noted significant TG accumulation in non-steatotic liver following IRI. This is in line with previous findings of transient steatosis following IRI (11) and partial hepatectomy (30). Of note, we did not see a similar increase in TG in steatotic liver.…”

Investigation of the hepatic development in the coculture of hiPSCs-derived LSECs and HLCs in a fluidic microenvironment

“…5(d) ]. Those results could be related to previously observed fatty liver patterns ( Lee et al , 2015 ) and are consistent with in vivo regenerative patterns in the liver ( Rudnick and Davidson, 2012 ). In the present work, higher expression of FADS3 was found in the proteomic dataset of coculture biochips.…”

Maternal Hepatocytes Heterogeneously and Dynamically Exhibit Developmental Phenotypes Partially via YAP1 during Pregnancy

“…This finding enabled us to gain some mechanistic insight into the regulation of pregnancydependent phenotypic plasticity in maternal hepatocytes. In addition, YAP1 has been reported to regulate lipid metabolism, and activation of YAP1 in hepatocytes causes fatty liver (47)(48)(49)(50). In this study, we observed that the absence of YAP1 in maternal hepatocytes decreased cholesterol concentrations in the maternal circulation, consistent with these studies.…”

Dynamic changes in the mouse hepatic lipidome following warm ischemia reperfusion injury

“…Specifically, we noted significant TG accumulation in non-steatotic liver following IRI. This is in line with previous findings of transient steatosis following IRI (11) and partial hepatectomy (30). Of note, we did not see a similar increase in TG in steatotic liver.…”

Investigation of the hepatic development in the coculture of hiPSCs-derived LSECs and HLCs in a fluidic microenvironment

“…5(d) ]. Those results could be related to previously observed fatty liver patterns ( Lee et al , 2015 ) and are consistent with in vivo regenerative patterns in the liver ( Rudnick and Davidson, 2012 ). In the present work, higher expression of FADS3 was found in the proteomic dataset of coculture biochips.…”

Maternal Hepatocytes Heterogeneously and Dynamically Exhibit Developmental Phenotypes Partially via YAP1 during Pregnancy

“…This finding enabled us to gain some mechanistic insight into the regulation of pregnancydependent phenotypic plasticity in maternal hepatocytes. In addition, YAP1 has been reported to regulate lipid metabolism, and activation of YAP1 in hepatocytes causes fatty liver (47)(48)(49)(50). In this study, we observed that the absence of YAP1 in maternal hepatocytes decreased cholesterol concentrations in the maternal circulation, consistent with these studies.…”