Chronic ingestion of ethanol stimulates lipogenic response in rat hepatocytes

Abstract

We isolated hepatocytes from rats chronically fed with ethanol and pair-fed control rats and incubated them both in the presence and absence of 100 mM ethanol in order to analyze the uptake into their lipids of several radiolabeled exogenous substrates. The hepatocytes treated chronically with ethanol showed higher lipogenic activity both in neutral lipids and phospholipids from serine, ethanolamine, glycerol and oleate. The only exception found was in the incorporation of choline into phosphatidylcholine (PC), which was lower in the hepatocytes from ethanol-fed rats than in the controls and was concomitant with a decrease in the PC levels of the ethanol-fed hepatocytes. The results obtained after exposing the cells to 100 mM ethanol in vitro indicate that in general the hepatocytes from ethanol-fed rats exhibit a higher lipogenic activity than the control cells. The only difference in the response to ethanol in vitro was found in the biosynthesis of phosphatidylserine (PS) from serine, which rose significantly in control cells but was unaffected in alcoholic hepatocytes. We put this difference in response down to specific adaptation to ethanol feeding.

WIF-B cells as a model for alcohol-induced hepatocyte injury

“…4), indicating that the accumulation of triglycerides was a result of ethanol metabolism. These data are in accordance with the development of fatty liver in hepatocytes isolated from rats chronically fed an ethanol-containing diet [26,27].…”

“…These effects are due to ethanol metabolism and are very similar to the reduced redox state and the development of fatty liver in hepatocytes after ethanol exposure [27,39]. Development of fatty liver is speculated to be the first step in developing alcoholic liver disease [24,26,27].…”

Role of Angiotensin Peptides Precursor in Ethanol Mediated Hepato toxicity: Perspective on Angiotensinogen

“…Hepatic fatty acid and triglycerides are increased after acute and chronic ethanol consumption [57]. Utilizing cell-based model, increased lipogenesis has been shown to occur due to higher expression and activation of lipogenic enzymes [58,59] [60,61]. SREBP-1c level is increased transcriptionally and by decreased proteasomal degradation of protein in acute and chronic alcohol exposure [62].…”

Role of phosphodiesterase-4 in alcohol-induced organ injury.

“…Alcohol induced hepatic steatosis is mediated by increased de novo lipogenesis and impaired fatty acid beta-oxidation [51]. Several studies have identified the genes involved in alcohol induced dysregulation of lipid metabolism leading to steatosis [52,53];…”

“…Hepatic lipid synthesis is accelerated after ethanol consumption and is associated with higher expression of lipogenic genes/enzymes, including fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACL), stearoyl CoA desaturase (SCD), and malic enzyme (ME) [52,53]. Sterol regulatory element binding protein-1c (SREBP-1c) is a transcription factor that plays an important role in regulating the expression of all alcohol induced lipogenic genes (e.g.…”