Choline deprivation: An overview of the major hepatic metabolic response pathways

Abstract

Choline (Ch) is an important nutrient that is involved in many physiological functions. Deprivation of Ch (CD) may lead to hepatocellular modifications and/or even hepatic tumorigenesis and it can be a frequent problem in clinical settings; it can accompany various common pathological (alcoholism and malnutrition) or physiological states (pregnancy and lactation). The aim of this review is to provide an up-to-date overview of the major metabolic pathways involved in the hepatic response toward the experimentally or clinically induced CD, and to shed more light on the implicated (and probably interrelated) mechanisms responsible for the observed hepatocellular modifications and/or carcinogenesis.

Review article: drug‐induced liver injury in the context of nonalcoholic fatty liver disease – a physiopathological and clinical integrated view

“…Insufficient amount of methyl‐group donors as a pathogenic mechanism associated with NAFLD progression has been supported by experimental and clinical evidences. A transgenic mouse model with deletion of genes needed to produce SAMe from methionine develops NAFLD, and a choline/methionine deficient diet leading to SAMe depletion is a common NAFLD model in rodents . In addition, SAMe‐mediated methylation of phosphatidylethanolamine is required for the correct VLDL assembly and secretion, a main pathway to export hepatic TGs .…”

“…A transgenic mouse model with deletion of genes needed to produce SAMe from methionine develops NAFLD, 240 and a choline/methionine deficient diet leading to SAMe depletion is a common NAFLD model in rodents. 241 In addition, SAMe-mediated methylation of phosphatidylethanolamine is required for the correct VLDL assembly and secretion, a main pathway to export hepatic TGs. 242 Oxidative stress is another major mechanism involved in MTX toxicity associated with folate depletion, since folate bears antioxidant mechanisms.…”

“Extracellular matrix remodelling in the liver of rats subjected to dietary choline deprivation and/or thioacetamide administration”

“…We have established that prolonged exposure to CDD and/or concomitant exposure to TAA causes progressive hepatic inflammation and fibrosis in rats . This type of hepatic injury includes gradual and progressive steatosis, stellate cell activation, fibrosis and a significant regenerative hepatocellular response that could simulate nonalcoholic fatty liver diseases . Combining the toxic effect of TAA with the detrimental dietary choline deprivation leads to progressive liver enzymes' stimulation and more severe liver damage, including cellular necrosis and apoptosis, followed by a significant regenerative response (with increasing mitotic figures to compensate cellular loss) .…”

“…This type of hepatic injury includes gradual and progressive steatosis, stellate cell activation, fibrosis and a significant regenerative hepatocellular response that could simulate nonalcoholic fatty liver diseases . Combining the toxic effect of TAA with the detrimental dietary choline deprivation leads to progressive liver enzymes' stimulation and more severe liver damage, including cellular necrosis and apoptosis, followed by a significant regenerative response (with increasing mitotic figures to compensate cellular loss) . Hepatic stellate cell activation is considered the main source of inflammatory mediators, including MMPs and their inhibitors, which have an important role in triggering fibrogenesis and inhibition of adequate nourishment to the newly regenerating cells, thus producing a picture of a micro‐ and macronodular fibrosis and, ultimately, cirrhosis …”

Liver Injury Models for Induction of Hepatic Oval Cells in Rodents

“…It is needed to form cellular membranes and is an important methyl-group donor necessary for converting homocysteine to methionine [95]. Choline deficiency leads to inflammation and oxidative stress, causing steatohepatitis and liver fibrosis.…”