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Alcohol Feeding (alcohol + feeding)

Distribution by Scientific Domains
Medical Sciences100%

Kinds of Alcohol Feeding

  • chronic alcohol feeding
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    Selected Abstracts

    Inhibition of adiponectin production by homocysteine: A potential mechanism for alcoholic liver disease,

    HEPATOLOGY, Issue 3 2008
    Zhenyuan Song
    Although recent evidence suggests that down-regulation of production of the adipocyte hormone adiponectin has pathophysiological consequences for the development of alcoholic liver disease (ALD), the underlying mechanisms are elusive. Abnormal hepatic methionine-homocysteine metabolism induced by prolonged alcohol exposure has been reported both in clinical and experimental studies of ALD. Here, we conducted both in vivo and in vitro experiments to examine the effects of prolonged alcohol exposure on homocysteine levels in adipose tissue, its potential involvement in regulating adiponectin production, and the consequences for ALD. Chronic alcohol exposure decreased the circulating adiponectin concentration and adiponectin messenger RNA (mRNA) and protein levels in epididymal fat pads. Alcohol feeding induced modest hyperhomocysteinemia and increased homocysteine levels in the epididymal fat pad, which was associated with decreased mRNA levels of cystationine ,-synthase. Betaine supplementation (1.5%, wt/vol) in the alcohol-fed mice reduced homocysteine accumulation in adipose tissue and improved adiponectin levels. Moreover, exogenous homocysteine administration reduced gene expression, protein levels, and secretion of adiponectin in primary adipocytes. Furthermore, rats fed a high-methionine diet (2%, wt/wt) were hyperhomocysteinemic and had decreased adiponectin levels in both plasma and adipose tissue, which was associated with suppressed AMP-activated protein kinase activation in the liver. Mechanistic studies revealed that both inactivation of the extracellular signal regulated kinase 1/2 pathway and induction of endoplasmic reticulum stress response, specifically C/EBP homologous protein expression, may contribute to the inhibitory effect exerted by homocysteine. Conclusion: Chronic alcohol feeding caused abnormal accumulation of homocysteine in adipocytes, which contributes to decreased adiponectin production in ALD. (HEPATOLOGY 2008.) [source]

    Cholinergic Mediation of Alcohol-Induced Experimental Pancreatitis

    ALCOHOLISM, Issue 10 2010
    Aurelia Lugea
    Objectives:, The mechanisms initiating pancreatitis in patients with chronic alcohol abuse are poorly understood. Although alcohol feeding has been previously suggested to alter cholinergic pathways, the effects of these cholinergic alterations in promoting pancreatitis have not been characterized. For this study, we determined the role of the cholinergic system in ethanol-induced sensitizing effects on cerulein pancreatitis. Methods:, Rats were pair-fed control and ethanol-containing Lieber-DeCarli diets for 6 weeks followed by parenteral administration of 4 hourly intraperitoneal injections of the cholecystokinin analog, cerulein at 0.5 ,g/kg. This dose of cerulein was selected because it caused pancreatic injury in ethanol-fed but not in control-fed rats. Pancreatitis was preceded by treatment with the muscarinic receptor antagonist atropine or by bilateral subdiaphragmatic vagotomy. Measurement of pancreatic pathology included serum lipase activity, pancreatic trypsin, and caspase-3 activities, and markers of pancreatic necrosis, apoptosis, and autophagy. In addition, we measured the effects of ethanol feeding on pancreatic acetylcholinesterase activity and pancreatic levels of the muscarinic acetylcholine receptors m1 and m3. Finally, we examined the synergistic effects of ethanol and carbachol on inducing acinar cell damage. Results:, We found that atropine blocked almost completely pancreatic pathology caused by cerulein administration in ethanol-fed rats, while vagotomy was less effective. Ethanol feeding did not alter expression levels of cholinergic muscarinic receptors in the pancreas but significantly decreased pancreatic acetylcholinesterase activity, suggesting that acetylcholine levels and cholinergic input within the pancreas can be higher in ethanol-fed rats. We further found that ethanol treatment of pancreatic acinar cells augmented pancreatic injury responses caused by the cholinergic agonist, carbachol. Conclusion:, These results demonstrate key roles for the cholinergic system in the mechanisms of alcoholic pancreatitis. [source]

    Anti-Inflammatory and Anti-Apoptotic Roles of Endothelial Cell STAT3 in Alcoholic Liver Injury

    ALCOHOLISM, Issue 4 2010
    Andrew M. Miller
    Background:, It is generally believed that the hepatoprotective effect of interleukin-6 (IL-6) is mediated via activation of signal transducer and activator of transcription 3 (STAT3) in hepatocytes. IL-6-deficient mice are more susceptible to alcohol-induced hepatocyte apoptosis and steatosis and elevation of serum alanine transaminase (ALT); however, whereas hepatocyte-specific STAT3 knockout mice are more susceptible to alcohol-induced hepatic steatosis, they have similar hepatocyte apoptosis and serum ALT after alcohol feeding compared with wild-type mice. This suggests that the hepatoprotective effect of IL-6 in alcoholic liver injury may be mediated via activation of STAT3-independent signals in hepatocytes, activation of STAT3 in nonparenchymal cells, or both. We have previously shown that IL-6 also activates STAT3 in sinusoidal endothelial cells (SECs). Thus, the purpose of this study was to investigate whether STAT3 in endothelial cells also plays a protective role in alcoholic liver injury. Methods:, Wild-type and endothelial cell-specific STAT3 knockout (STAT3E,/,) mice were pair-fed and fed ethanol containing diet for 4 weeks. Liver injury and inflammation were determined. Results:, Feeding mice with ethanol-containing diet for 4 weeks induced greater hepatic injury (elevation of serum ALT) and liver weight in STAT3E,/, mice than wild-type control groups. In addition, ethanol-fed STAT3E,/, mice displayed greater hepatic inflammation and substantially elevated serum and hepatic levels of IL-6 and TNF-, compared with wild-type mice. Furthermore, ethanol-fed STAT3E,/, mice displayed a greater abundance of apoptotic SECs and higher levels of serum hyaluronic acid than wild-type controls. Conclusions:, These data suggest that endothelial cell STAT3 plays important dual functions of attenuating hepatic inflammation and SEC death during alcoholic liver injury. [source]

    Chronic Alcohol Consumption Disrupted Cholesterol Homeostasis in Rats: Down-Regulation of Low-Density Lipoprotein Receptor and Enhancement of Cholesterol Biosynthesis Pathway in the Liver

    ALCOHOLISM, Issue 3 2010
    Zhigang Wang
    Background:, Chronic alcohol consumption causes alcoholic liver disease, which is associated, or initiated, with dysregulated lipid metabolism. Very recent evidence suggested that dysregulated cholesterol metabolism plays an important role in the pathogenesis of alcoholic fatty liver diseases, however, the effects of chronic alcohol exposure on cholesterol homeostasis have not been well studied and underlying mechanisms behind are still elusive. Methods:, Male Sprague,Dawley rats weighing 250 ± 5.5 g (mean ± SEM) divided into 2 groups (8 rats per group) and pair-fed with liquid diets containing (in percent of energy intake) 18% protein, 35% fat, 12% carbohydrate, and 35% either ethanol (ethanol diet) or an isocaloric maltose-dextrin mixture (control diet), according to Lieber and De Carli, for 4 weeks. Results:, Long-term excessive alcohol feeding to rats caused fatty liver and liver injury, which was associated with disrupted cholesterol homeostasis, characterized by increased hepatic cholesterol levels and hypercholesterolemia. Hepatic cholesterol increases were concomitant with constantly activated sterol regulatory element-binding protein-2 (SREBP-2) in the liver and increased expression of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, a rate-limiting enzyme for cholesterol de novo synthesis, indicating enhanced cholesterol biosynthesis. Alcohol-induced hypercholesterolemia was accompanied by decreased LDL receptor (LDLr) levels in the liver. Further investigations revealed that chronic alcohol exposure increased hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) contents to down-regulate LDLr via a post-translational mechanism. Moreover, alcohol feeding suppressed extracellular signal-regulated kinase (ERK) activation in the liver. In vitro studies showed that inhibition of ERK activation was associated with decreased LDLr expression in HepG2 cells. Conclusions:, Our study provides the first evidence that both increased PCSK9 expression and suppressed ERK activation in the liver contributes to alcohol-induced hypercholesterolemia in rats. [source]

    Mitochondrial S -Adenosyl- l -Methionine Transport is Insensitive to Alcohol-Mediated Changes in Membrane Dynamics

    ALCOHOLISM, Issue 7 2009
    Anna Fernández
    Background:, Alcohol-induced liver injury is associated with decreased S -adenosyl- l -methionine (SAM)/S -adenosyl- l -homocysteine (SAH) ratio and mitochondrial glutathione (mGSH) depletion, which has been shown to sensitize hepatocytes to tumor necrosis factor (TNF). Aims:, As the effect of alcohol on mitochondrial SAM (mSAM) has been poorly characterized, our aim was to examine the status and transport of mSAM in relation to that of mGSH during alcohol intake. Methods:, Sprague,Dawley rats were pair fed Lieber,DeCarli diets containing alcohol for 1 to 4 weeks and liver fractionated into cytosol and mitochondria to examine the mSAM transport and its sensitivity to membrane dynamics. Results:, We found that cytosol SAM was depleted from the first week of alcohol feeding, with mSAM levels paralleling these changes. Cytosol SAH, however, increased during the first 3 weeks of alcohol intake, whereas its mitochondrial levels remained unchanged. mGSH depletion occurred by 3 to 4 weeks of alcohol intake due to cholesterol-mediated impaired transport from the cytosol. In contrast to this outcome, the transport of SAM into hepatic mitochondria was unaffected by alcohol intake and resistant to cholesterol-mediated perturbations in membrane dynamics; furthermore cytosolic SAH accumulation in primary hepatocytes by SAH hydrolase inhibition reproduced the mSAM depletion by alcohol due to the competition of SAH with SAM for mitochondrial transport. However, alcohol feeding did not potentiate the sensitivity to inhibition by SAH accumulation. Conclusions:, Alcohol-induced mSAM depletion precedes that of mGSH and occurs independently of alcohol-mediated perturbations in membrane dynamics, disproving an inherent defect in the mSAM transport by alcohol. These findings suggest that the early mSAM depletion may contribute to the alterations of mitochondrial membrane dynamics and the subsequent mGSH down-regulation induced by alcohol feeding. [source]

    Acute Alcohol Intoxication Increases REDD1 in Skeletal Muscle

    ALCOHOLISM, Issue 5 2008
    Charles H. Lang
    Background:, The mechanism by which acute alcohol (EtOH) intoxication decreases basal muscle protein synthesis via inhibition of the Ser/Thr kinase mammalian target of rapamycin (mTOR) is poorly defined. In this regard, mTOR activity is impaired after over expression of the regulatory protein REDD1. Hence, the present study assessed the ability of REDD1 as a potential mediator of the EtOH-induced decrease in muscle protein synthesis. Methods:, The effect of acute EtOH intoxication on REDD1 mRNA and protein was determined in striated muscle of rats and mouse myocytes using an RNase protection assay and Western blotting, respectively. Other components of the mTOR signaling pathway were also assessed by immunoblotting. For comparison, REDD1 mRNA/protein was also determined in the muscle of rats chronically fed an alcohol-containing diet for 14 weeks. Results:, Intraperitoneal (IP) injection of EtOH increased gastrocnemius REDD1 mRNA in a dose- and time-dependent manner, and these changes were associated with reciprocal decreases in the phosphorylation of 4E-BP1, which is a surrogate marker for mTOR activity and protein synthesis. No change in REDD1 mRNA was detected in the slow-twitch soleus muscle or heart. Acute EtOH produced comparable increases in muscle REDD1 protein. The EtOH-induced increase in gastrocnemius REDD1 was independent of the route of EtOH administration (oral vs. IP), the nutritional state (fed vs. fasted), gender, and age of the rat. The nonmetabolizable alcohol tert -butanol increased REDD1 and the EtOH-induced increase in REDD1 was not prevented by pretreatment with the alcohol dehydrogenase inhibitor 4-methylpyrazole. In contrast, REDD1 mRNA and protein were not increased in the isolated hindlimb perfused with EtOH or in C2C12 myocytes incubated with EtOH, under conditions previously reported to decrease protein synthesis. Pretreatment with the glucocorticoid receptor antagonist RU486 failed to prevent the EtOH-induced increase in REDD1. Finally, the EtOH-induced increase in REDD1 was not associated with altered formation of the TSC1,TSC2 complex or the phosphorylation of TSC2 which is down stream in the REDD1 stress response pathway. In contradistinction to the changes observed with acute EtOH intoxication, REDD1 mRNA/protein was not changed in gastrocnemius from chronic alcohol-fed rats despite the reduction in 4E-BP1 phosphorylation. Conclusions:, These data indicate that in fast-twitch skeletal muscle (i) REDD1 mRNA/protein is increased in vivo by acute EtOH intoxication but not in response to chronic alcohol feeding, (ii) elevated REDD1 in response to acute EtOH appears due to the production of an unknown secondary mediator which is not corticosterone, and (iii) the EtOH-induced decrease in protein synthesis can be dissociated from a change in REDD1 suggesting that the induction of this protein is not responsible for the rapid decrease in protein synthesis after acute EtOH administration or for the development of alcoholic myopathy in rats fed an alcohol-containing diet. [source]

    Increased Lipopolysaccharide Sensitivity in Alcoholic Fatty Livers Is Independent of Leptin Deficiency and Toll-Like Receptor 4 (TLR4) or TLR2 mRNA Expression

    ALCOHOLISM, Issue 6 2005
    Laszlo Romics Jr
    Background: Both alcoholic (AFL) and nonalcoholic (NAFL) fatty livers show increased sensitivity to endotoxin-induced injury. Lipopolysaccharide (LPS) is recognized by toll-like receptor 4 (TLR4), whereas lipopeptide triggers TLR2 to induce common downstream activation of nuclear factor (NF)-,B and pro-inflammatory pathways that are activated in AFL and NAFL. Methods: Serum alanine aminotransferase (ALT), tumor necrosis factor (TNF)-,, and interleukin (IL)-6 levels; hepatic NF-,B activity; and expression of TLR2, TLR4, inducible nitric oxide synthase (iNOS), and heme oxygenase (HO)-1 mRNAs were investigated in lean and leptin-deficient ob/ob mice after LPS challenge in combination with acute or chronic alcohol feeding. Results: Increased LPS sensitivity in AFL and NAFL was characterized by elevated serum TNF-, and IL-6 induction. However, there was no difference in TLR2 and TLR4 mRNA levels between lean and ob/ob livers at baseline and after acute or chronic alcohol treatment. LPS increased TLR2, but not TLR4, mRNA levels in all groups. Chronic alcohol feeding and LPS increased serum ALT and TNF-, levels in lean but not in ob/ob mice compared with pair-fed controls. Hepatic NF-,B activation was increased in both ob/ob and lean mice after chronic alcohol feeding compared with pair-fed controls. Expression of iNOS, an inducer of oxidative stress, and HO-1, a cytoprotective protein, were higher in ob/ob compared with lean mice after chronic alcohol feeding. However, LPS-induced HO-1, but not iNOS, expression was attenuated in ob/ob compared with lean mice. Conclusion: These results imply that the increased sensitivity of AFL to LPS occurs without up-regulation of TLR2 or TLR4 genes and may be related to an imbalance of pro-inflammatory/oxidative and cytoprotective mechanisms. [source]

    Inhibition of Alcohol-Associated Colonic Hyperregeneration by ,-Tocopherol in the Rat

    ALCOHOLISM, Issue 1 2003
    P. Vincon
    Background: Chronic alcohol consumption results in colorectal mucosal hyperregeneration, a condition associated with an increased risk for colorectal cancer. Possible mechanisms may involve the effects of acetaldehyde and/or free radicals generated during alcohol metabolism. Vitamin E is part of the antioxidative defense system, and its concentration is decreased or its metabolic utilization increased in various tissues after chronic alcohol consumption. We wondered whether ,-tocopherol supplementation may prevent ethanol-induced colorectal cell cycle behavior and whether these changes were related to alterations in protein synthesis. Methods: Five groups of male Wistar rats, each consisting of 14 animals, received liquid diets as follows: group 1, alcohol; group 2, alcohol +,-tocopherol; group 3, control (i.e., isocaloric glucose); group 4; control (i.e., isocaloric glucose) +,-tocopherol. Group 5 was fed a solid chow diet ad libitum. After 4 weeks of feeding, immunohistology was performed with anti-proliferating cell nuclear antigen (PCNA) or anti-BCL2 antibodies. Fractional (ks) and absolute (Vs) rates of protein synthesis and rates of protein synthesis relative to RNA (kRNA) and DNA (kDNA) were measured with a flooding dose of L-[4- 3H] phenylalanine with complementary analysis of protein and nucleic acid composition. Results: The PCNA index was increased significantly in the colon after ethanol administration compared with controls (ethanol, 10.3 ± 2.3 vs. control, 6.51 ± 1.6% PCNA positive cells, p < 0.05), although neither the protein, RNA, and DNA concentrations nor ks, kRNA, kDNA, and Vs were affected. This increase in PCNA index was significantly diminished by coadministration of ,-tocopherol (ethanol +, - tocopherol, 7.86 ± 1.71% PCNA positive cells, p < 0.05) without significant alterations in protein synthetic parameters. A similar result was obtained for the PCNA index in the rectal mucosa (ethanol, 14.6 ± 4.4 vs. control, 12.1 ± 4.2% PCNA positive cell), although this did not reach statistical significance. Neither ethanol nor , - tocopherol feeding had any significant effect on BCL-2 expression in the colorectal mucosa. As with the colon, protein synthetic parameters in the mucosa were not affected by alcohol feeding at 4 weeks. These effects on colonic cell turnover without corresponding changes in protein synthesis thus represent a specific localized phenomenon rather than a general increase in anabolic processes in the tissue and reaffirm the hyperregenerative properties of chronic alcohol consumption. Conclusions: Alcohol-associated hyperproliferation could be prevented, at least in part, by supplementation with ,-tocopherol. This may support the hypothesis that free radicals are involved in the pathogenesis of alcohol-associated colorectal hyperproliferation. [source]