Effect of prolonged ethanol ingestion on hepatic lipogenesis and related enzyme activities.
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ABSTRACT:
SUBMITTER: Savolainen MJ
PROVIDER: S-EPMC1164771 | biostudies-other | 1977 Apr
REPOSITORIES: biostudies-other
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Project description:Alcoholic liver disease (ALD) is a prominent cause of morbidity and mortality in the United States. Alterations in protein folding occur in numerous disease states, including ALD. The endoplasmic reticulum (ER) is the primary site of post-translational modifications (PTM) within the cell. Glycosylation, the most abundant PTM, affects protein stability, structure, localization, and activity. Decreases in hepatic glycosylation machinery have been observed in rodent models of ALD, but specific protein targets have not been identified. Utilizing two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry, glycoproteins were identified in hepatic microsomal fractions from control and ethanol-fed mice. This study reports for the first time a global decrease in ER glycosylation. Additionally, the identification of 30 glycoproteins within this fraction elucidates pathway-specific alterations in ALD impaired glycosylation. Among the identified proteins, triacylglycerol hydrolase (TGH) is positively affected by glycosylation, showing increased activity following the addition of sugar moieties. Impaired TGH activity is associated with increased cellular storage of lipids and provides a potential mechanism for the observed pathologies associated with ALD.
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Project description:BackgroundTaste and appreciation of sports drinks can affect perceived exertion during exercise. Anecdotal evidence shows that maple products are regularly consumed by recreational and professional athletes but very few studies have reported on their effects during exercise. The purpose of the current study is to report the taste, appreciation and perceived exertion following the ingestion of maple-based sports drinks and other carbohydrate drinks during prolonged exercise.MethodsRecreationally and competitively active male subjects (n = 76, mass = 73.7 ± 10.3 kg, maximum oxygen consumption (VO2max) = 4.4 ± 0.5 L/min, maximal aerobic power (MAP) = 309 ± 42 W) ingested one of four carbohydrate solutions (all at 60 g CHO/L): concentrated maple sap (MW), diluted maple syrup (MS), glucose (G), a commercial sports drink (CSD), or a placebo (P; water sweetened with stevia) at every 30 min during 120 min of steady-state exercise (SSE) on a cycle ergometer at 66% MAP. Ratings of perceived exertion (RPE, Borg CR-10) were recorded at each 30 min throughout SSE. A questionnaire was administered to assess sensory characteristics (sweetness, acidity, refreshing, and overall taste on a visual analogue scale, converted to decimals from 0 to 1) and appreciation (sweet, acid and overall on a 9-point hedonic scale) 30 min before (immediately after the first ingestion) and immediately after SSE.ResultsSweetness was perceived to be higher for MW than G and P (pre: 0.60 ± 0.19, 0.51 ± 0.17 and 0.50 ± 0.17 and post: 0.69 ± 0.19, 0.34 ± 0.18 and 0.48 ± 0.22; p < 0.05, respectively) and MS was rated higher than MW for the appreciation of the sweet taste (pre: 6.5 ± 1.5 vs. 4.6 ± 1.8 and post: 6.8 ± 1.8 and 4.1 ± 1.8; p < 0.05, respectively). Furthermore, subjects that had ingested MW, reported a significantly lower RPE than those with P at 120 min (14.1 ± 2.2 vs. 16.0 ± 2.0, respectively).ConclusionsA sports drink containing maple syrup is well appreciated during prolonged exercise and appears to be a viable alternatives to more common sources of carbohydrates.Trial registrationNCT02880124 . Registered on 26 August 2016.
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Project description:Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMGCoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.
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Project description:Both frugivores and nectarivores are potentially exposed to dietary ethanol produced by fermentative yeasts which metabolize sugars. Some nectarivorous mammals exhibit a preference for low-concentration ethanol solutions compared to controls of comparable caloric content, but behavioural responses to ethanol by nectar-feeding birds are unknown. We investigated dietary preference by Anna's Hummingbirds (Calypte anna) for ethanol-enhanced sucrose solutions. Via repeated binary-choice experiments, three adult male hummingbirds were exposed to sucrose solutions containing 0%, 1% or 2% ethanol; rates of volitional nectar consumption were measured over a 3 h interval. Hummingbirds did not discriminate between 0% and 1% ethanol solutions, but exhibited significantly reduced rates of consumption of a 2% ethanol solution. Opportunistic measurements of ethanol concentrations within hummingbird feeders registered values peaking at about 0.05%. Ethanol at low concentrations (i.e. up to 1%) is not aversive to Anna's Hummingbirds and may be characteristic of both natural and anthropogenic nectars upon which they feed. Given high daily amounts of nectar consumption by hummingbirds, chronic physiological exposure to ethanol can thus be substantial, although naturally occurring concentrations within floral nectar are unknown.
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Project description:The objective of this study was to evaluate the age-related changes in antioxidant status and the lipid metabolism of pigeon squabs (Columba livia), by determining the BW, antioxidant indices, serum lipid levels, lipid metabolism-related enzyme activities, lipid metabolism-related gene expression, and liver morphology in squabs. Ten squabs were randomly selected and sampled on the day of hatching (DOH), days 7 (D7), 14 (D14) and 21 (D21) post-hatch, respectively. The results showed that BW of squabs increased linearly from DOH to D21. The minimum fold of BW gain was observed in the phase from D14 to D21. Serum triglyceride and free fatty acid levels displayed linear and quadratic trends as age increased, with these maximum responses in D14. Serum low-density lipoprotein cholesterol level responded to age linearly and quadratically with the minimum in D14. Serum high-density lipoprotein cholesterol level and the ratio of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol increased linearly with age, whereas the very low-density lipoprotein cholesterol level decreased linearly. The activities of glutathione peroxidase, catalase, and superoxide dismutase in liver displayed linear and quadratic trends as age increased, with these minimum responses in D14. Hepatic malondialdehyde concentration responded to age linearly and quadratically, with the maximum in D14. Activities of lipoprotein lipase, hepatic lipase, and 3-hydroxy-3-methyl glutaryl coenzyme A reductase in liver responded to age linearly and quadratically, with these minimum responses in D14. Hepatic hormone-sensitive lipase activity displayed linear and quadratic trends as age increased with the maximum in D14. Hepatic acetyl CoA carboxylase activity on D14 was significantly lower than squabs on DOH and D7. Hepatic carnitine palmitoyltransferase 1 mRNA expression responded to age linearly and quadratically, with minimum response in D14. Hepatic mRNA expression of acetyl CoA carboxylase and fatty acid synthetase increased linearly with age. Hepatic Oil-Red-O staining area displayed a quadratic trend as age increased, with the maximum response in D14. In conclusion, the phase from DOH to D14 was a crucial development stage for growth, antioxidant status and lipid metabolism in pigeon squabs. The results suggest it is better to take nutritional manipulation in squabs before D14.
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Project description:This study evaluated the antilipogenic and anti-inflammatory effects of Codonopsis lanceolata (C. lanceolata) root extract in mice with alcohol-induced fatty liver and elucidated its underlying molecular mechanisms. Ethanol was introduced into the liquid diet by mixing it with distilled water at 5% (wt/v), providing 36% of the energy, for nine weeks. Among the three different fractions prepared from the C. lanceolata root, the C. lanceolata methanol extract (CME) exhibited the most remarkable attenuation of alcohol-induced fatty liver with respect to various parameters such as hepatic free fatty acid concentration, body weight loss, and hepatic accumulations of triglyceride and cholesterol. The hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively. CME feeding significantly restored the ethanol-induced downregulation of the adiponectin receptor (adipoR) 1 and of adipoR2, along with their downstream molecules. Furthermore, the study data showed that CME feeding dramatically reversed ethanol-induced hepatic upregulation of toll-like receptor- (TLR-) mediated signaling cascade molecules. These results indicate that the beneficial effects of CME against alcoholic fatty livers of mice appear to be with adenosine- and adiponectin-mediated regulation of hepatic steatosis and TLR-mediated modulation of hepatic proinflammatory responses.
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Project description:Alcohol dependence is linked to dysregulation of the hypothalamic-pituitary-adrenal axis. Here, we investigated effects of repeated ethanol intoxication-withdrawal cycles (using chronic intermittent ethanol vapor inhalation; CIE) and abstinence from CIE on peak and nadir plasma corticosterone (CORT) levels. Irritability- and anxiety-like behaviors as well as glucocorticoid receptors (GR) in the medial prefrontal cortex (mPFC) were assessed at various intervals (2h-28d) after cessation of CIE. Results show that peak CORT increased during CIE, transiently decreased during early abstinence (1-11d), and returned to pre-abstinence levels during protracted abstinence (17-27d). Acute withdrawal from CIE enhanced aggression- and anxiety-like behaviors. Early abstinence from CIE reduced anxiety-like behavior. mPFC-GR signaling (indexed by relative phosphorylation of GR at Ser211) was transiently decreased when measured at time points during early and protracted abstinence. Further, voluntary ethanol drinking in CIE (CIE-ED) and CIE-naïve (ED) rats, and effects of CIE-ED and ED on peak CORT levels and mPFC-GR were investigated during acute withdrawal (8h) and protracted abstinence (28d). CIE-ED and ED increased peak CORT during drinking. CIE-ED and ED decreased expression and signaling of mPFC-GR during acute withdrawal, an effect that was reversed by systemic mifepristone treatment. CIE-ED and ED demonstrate robust reinstatement of ethanol seeking during protracted abstinence and show increases in mPFC-GR expression. Collectively, the data demonstrate that acute withdrawal from CIE produces robust alterations in GR signaling, CORT and negative affect symptoms which could facilitate excessive drinking. The findings also show that CIE-ED and ED demonstrate enhanced relapse vulnerability triggered by ethanol cues and these changes are partially mediated by altered GR expression in the mPFC. Taken together, transition to alcohol dependence could be accompanied by alterations in mPFC stress-related pathways that may increase negative emotional symptoms and increase vulnerability to relapse.
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Project description:Regulation of lipid droplets (LDs) metabolism is the core of controlling intracellular fatty acids (FAs) fluxes, and perilipin 5 (PLIN5) plays a key role in this process. Our previous studies have found that hepatic PLIN5 deficiency reduces LDs accumulation, but the trafficking of FAs produced from this pathway and the interaction between mitochondria and LDs in this process are largely unknown. Here, we found that the deficiency of PLIN5 decreases LDs accumulation by increasing FAs efflux. In addition, the decreased lipogenesis of PLIN5-deficient hepatocytes is accompanied by mitochondrial dysfunction, suggesting that PLIN5 plays an important role in mediating the interaction between LDs and mitochondria. Importantly, PLIN5 ablation negates oxidative capacity differences of peri-droplet and cytosolic mitochondria. In summary, these data indicate that PLIN5 plays a vital role in maintaining mitochondrial-mediated lipogenesis, which provides an important new perspective on the regulation of liver lipid storage and the relationship between PLIN5 and mitochondria.
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Project description:ObjectiveGiven the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity.Research design and methodsMale C57BL/6J mice were fed a high-fat/high-sucrose diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4-20 weeks. A total of 5% EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and HF + EPA groups.ResultsBoth the HF/HS and HF groups similarly developed obesity. EPA treatment strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where hepatic triglyceride content and lipogenic enzymes are increased. There is no appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of reducing hepatic triglyceride secretion and changing VLDL fatty acid composition in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is capable of increasing energy consumption in the HF/HS + EPA group.ConclusionsThis study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis. Because the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data suggest that EPA is suited for treatment of the metabolic syndrome.
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Project description:Withdrawal anxiety following chronic ethanol exposure is often associated with relapse in recovering alcoholics. It is likely that brain regions regulating anxiety-like behaviors adapt during chronic ethanol exposure to ultimately regulate such behaviors. The central amygdala contains numerous neurotransmitter systems that have been implicated in the regulation of anxiety-like behavior, including corticotropin releasing factor (CRF) and NMDA-type glutamate receptors. Chronic ethanol exposure causes functional adaptations in both CRF and NMDA receptors that are likely to regulate anxiety-like behaviors expressed during withdrawal. However, the molecular mechanisms governing these adaptations remain unexplored. We therefore evaluated these neurotransmitter systems in Sprague-Dawley rats during chronic ingestion of an ethanol-containing liquid diet. Quantitative real-time reverse transcription-PCR demonstrated that preproCRF mRNA was significantly upregulated by chronic ethanol exposure, whereas mRNA expression of CRF binding protein did not change. There were also no significant changes observed in any of the NMDA subunit mRNAs, although there was a trend toward greater NR2A mRNA expression during chronic ethanol exposure. Using Western blotting analysis we measured NMDA receptor subunit protein expression. Chronic ethanol exposure did not affect protein levels of the NR1 and NR2B subunits. Like the mRNA measures, chronic ethanol exposure did influence NR2A protein levels but the effects were modest. Our results demonstrate that NMDA receptor subunit mRNA and protein expressions are not strongly influenced by exposure to chronic ethanol. This suggests that the functional NMDA receptor adaptations identified in previous studies [Roberto, M., Schweitzer, P., Madamba, S. G., Stouffer, D. G., Parsons, L. H., & Siggins, G. R. (2004). Acute and chronic ethanol exposure alter glutamatergic transmission in rat central amygdala: an in vitro and in vivo analysis. J Neurosci 24, 1594-1603] are likely to be mediated by post-translational events. In contrast, enhanced levels of CRF during/after chronic ethanol exposure are likely to be mediated by increased levels of prepro CRF mRNA. Together, our findings suggest that adaptations to chronic ethanol exposure by proanxiety factors expressed in the central nucleus appear to be mediated by distinct cellular and molecular mechanisms.
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