Biochemical aspects associated with an ethanol-induced fatty liver

Walker, Jennifer E. C.; Gordon, Ellen R.

doi:10.1042/bj1190511

Cited by 43 publications

(13 citation statements)

References 21 publications

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“…This hypothesis is supported by the observation that glycogen stores are depressed after ethanol feeding [22], For example, in perfused livers which were freeze-clamped during 7EC metabo lism, glycogen levels were 12.1 pmol/g in liv ers from ethanol-fed rats, compared to 35.8 pmol/g in controls (data not shown). As a result of diminished glycogen stores, sub strate supply for the pentose phosphate cycle may become limiting.…”

Section: Thurman and Scholzsupporting

confidence: 69%

7-Ethoxycoumarin O-Deethylation in Perfused Livers from Ethanol-Fed Rats: Evidence for an Important Role of Mitochondrial Reducing Equivalents

Reinke¹,

Tupper²,

Sweeny³

1987

Pharmacology

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Rates of 7-ethoxycoumarin (7EC) O-deethylation in perfused livers were increased approximately 3-fold by chronic ethanol feeding. The acute addition of ethanol (5 mM) and antimycin A (0.03 mM) strongly inhibited 7EC metabolism in perfused livers from ethanol-fed rats, but less inhibition was observed when these agents were added to microsomes or to perfused livers from control rats. The activity of the hepatic pentose phosphate cycle in perfused livers was assessed by comparing ¹⁴CO₂ release during the infusion of 1-¹⁴C-glucose or 6-¹⁴C-glucose. 7EC infusion caused a 3-fold greater increase in ¹⁴CO₂ production from 1-¹⁴C-glucose in a liver from a control rat than in a liver from an ethanol-fed rat, indicating greater hepatic pentose cycle activity in livers of control rats. Thus, the pronounced inhibition of 7EC metabolism caused by infusion of ethanol and antimycin A may be explained by a greater dependency on mitochondrial sources of NADPH in livers of ethanol-fed rats. Dinitrophenol (0.05 mM) did not inhibit 7EC metabolism in perfused livers, indicating that a reduction in the cellular redox state, and not diminished energetics, is involved in the mechanism of inhibition produced by antimycin A.

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Section: Thurman and Scholzsupporting

confidence: 69%

7-Ethoxycoumarin O-Deethylation in Perfused Livers from Ethanol-Fed Rats: Evidence for an Important Role of Mitochondrial Reducing Equivalents

Reinke¹,

Tupper²,

Sweeny³

1987

Pharmacology

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“…Previous studies report that acute and chronic ethanol consumption reduce liver glycogen content (28,46,50,52); however, the mechanisms responsible for this adverse metabolic outcome are not known. Herein, we evaluated the impact chronic ethanol consumption has on diurnal oscillations in various glycogen metabolic processes using a mouse model.…”

Section: Discussionmentioning

confidence: 95%

“…Notably, ethanol-induced decreases in hepatic glycolytic activity are paralleled by significant decreases in liver glycogen levels (47). Several studies have shown that both acute and chronic alcohol consumption reduce hepatic glycogen levels (28,46,47,50,52,53). However, the mechanisms underlying these ethanol-mediated effects on liver glycogen metabolism remain poorly understood.…”

mentioning

confidence: 99%

Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice

Udoh

Swain

Filiano

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease.

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“…ATP dependent transport across membranes is in fluenced by ethanol. The chronic ingestion of ethanol by rats increases their hepatic activity of Mg++ stimulated adenosine triphosphatase with a fall in the hepatic concentration of ATP and a rise in Pi [Walker and G ordon, 1970], However, oxygen consumption under these conditions has not been determined. Inappropriate vasodilatation of superficial ves sels could increase the loss of heat that can only be replaced by an in creased catabolic rate.…”

Section: Discussionmentioning

confidence: 99%

The Energy Cost of the Metabolism of Drugs, Including Ethanol

Pirola

Cs²

1972

Pharmacology

192

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Observations of changes in body weight in man and rats indicate that the administration of high doses of ethanol results in an inefficient utilization of calories. It is postulated that this is due, at least in part, to activation of energy wasteful metabolic pathways such as microsomal ethanol oxidizing system (MEOS) in the hepatic endoplasmic reticulum, that this effect is increased by microsomal enzyme proliferation induced by ethanol consumption, and that the energy balance may be similarly disturbed by administration of other drugs. The proposed mechanism for these changes is an increase in the microsomal oxidation of both substrates (such as ethanol) and of NADPH, a process which does not appear to be linked to energy conservation such as the production of ATP. In the case of ethanol, these effects would be expected to be most obvious during ingestion of moderately high doses because of the much higher Km of ethanol for MEOS than for ADH. Because of the ability of ethanol feeding to induce various microsomal enzyme activities, the metabolism of substrates other than ethanol may also be involved in the energy wasting process.

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Biochemical aspects associated with an ethanol-induced fatty liver

Cited by 43 publications

References 21 publications

7-Ethoxycoumarin O-Deethylation in Perfused Livers from Ethanol-Fed Rats: Evidence for an Important Role of Mitochondrial Reducing Equivalents

7-Ethoxycoumarin O-Deethylation in Perfused Livers from Ethanol-Fed Rats: Evidence for an Important Role of Mitochondrial Reducing Equivalents

Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice

The Energy Cost of the Metabolism of Drugs, Including Ethanol

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