Effects of dietary genistein on hepatic lipid metabolism and mitochondrial function in mice fed high-fat diets

OBJECTIVE: Genistein has been suggested to prevent insulin resistance and its related diseases. We investigated the effects of dietary genistein at different levels on hepatic lipid levels and mitochondrial functions in mice fed high-fat diets. METHODS: C57BL/6J mice were randomly divided into four groups and fed a high-fat diet containing genistein at levels of 0%, 0.1%, 0.2%, and 0.4% (HF, HF + 0.1G, HF + 0.2G, and HF + 0.4G) for 12 wk. We measured lipid levels in the blood and liver. We also observed messenger RNA (mRNA) expression of genes encoding proteins related to lipid and energy metabolism and antioxidant defense system and mitochondrial enzyme activities in the liver. RESULTS: The induction of fatty liver by HF was substantially decreased in the HF + 0.2G and HF + 0.4G groups. Peroxisome proliferator-activated receptorgamma coactivator mRNA was increased by HF + 0.4G. Although genistein did not affect peroxisomal acyl-CoA oxidase mRNA expression, it increased medium-chain acyl-CoA dehydrogenase mRNA expression in a dose-dependent manner and HF + 0.2G increased uncoupling protein-2 mRNA expression two-fold relative to HF mice. Genistein decreased malondialdehyde levels and increased glutathione levels in liver homogenates, regardless of dose. The HF + 0.1G diet increased mitochondrial glutathione peroxidase activity and mitochondrial succinate dehydrogenase activity. CONCLUSIONS: Although genistein at higher levels decreased hepatic fat accumulation possibly by increasing fatty acid oxidation and uncoupling protein, low-dose genistein increased mitochondrial enzyme activities in mice with fatty liver and obesity induced by high-fat diets.     

Liver antioxidant defenses in mice fed ethanol and the AIN-76A diet

The effects of chronic alcohol (EtOH) ingestion on antioxidant defenses in mice fed AIN-76A liquid diets were investigated. C57B1/6 female mice were divided into three groups and fed the AIN-76A liquid EtOH diet containing EtOH to provide 31% of total caloric intake (TCI), the same basic diet containing EtOH to provide 35% of TCI, or an isocaloric AIN-76A liquid control diet. After 3 weeks, the mice were killed and livers were excised for biochemical analysis. Liver reduced glutathione (GSH) levels, and activities of both Mn-Superoxide dismutase (SOD) and Cu/Zn-SOD were significantly decreased by both levels of EtOH. Activities of catalase and glutathione transferase (GT) were significantly increased, whereas glutathione peroxidase (GP) activity was not affected by either level of EtOH. Our previous study using the Lieber-DeCarli liquid EtOH diet caused a decline of total SOD and GP activities. The results suggest that chronic EtOH administration decreases liver antioxidant defenses; however, the mice fed the AIN-76A EtOH liquid diet can maintain a higher antioxidant defense capability than those fed Lieber-DeCarli EtOH liquid diet.     

Acetyl-l-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease

Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-l-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial β-oxidation. We hypothesized that oral administration ALC with the antioxidant lipoic acid (ALC + LA) would benefit nonalcoholic fatty liver. To test our hypothesis, we fed Balb/C mice a standard diet (SF) or SF with ALC + LA or high-fat diet (HF) or HF with ALC + LA for 6 months. Acetyl-l-carnitine and LA were dissolved at 0.2:0.1% (wt/vol) in drinking water, and mice were allowed free access to food and water. Along with physical parameters, insulin resistance (blood glucose, insulin, glucose tolerance), liver function (alanine transaminase [ALT], aspartate transaminase [AST]), liver histology (hematoxylin and eosin), oxidative stress (malondialdehyde), and mitochondrial abnormalities (carbamoyl phosphate synthase 1 and electron microscopy) were done. Compared with SF, HF had higher body, liver, liver-to-body weight ratio, white adipose tissue, ALT, AST, liver fat, oxidative stress, and insulin resistance. Coadministration of ALC + LA to HF animals significantly improved the mitochondrial marker carbamoyl phosphate synthase 1 and the size of the mitochondria in liver. Alanine transaminase and AST levels were decreased. In a nonalcoholic fatty liver mice model, ALC + LA combination improved liver mitochondrial content, size, serum ALT, and AST without significant changes in oxidative stress, insulin resistance, and liver fat accumulation.     

Açaí seed extract prevents the renin-angiotensin system activation,oxidative stress and inflammation in white adipose tissue of high-fat diet–fed mice

The role of the renin-angiotensin system (RAS), oxidative stress, and inflammation on the development of obesity and its comorbidities has been extensively addressed. Euterpe oleracea Mart. (açaí) seed extract (ASE), with antioxidant and anti-inflammatory properties and capable to modulate plasma renin levels, has been evidenced as a potential regulator of body mass. We hypothesized that the supplementation with ASE might exert beneficial effects on obesity-related white adipose tissue changes and metabolic disorders by interfering with the local adipose tissue overexpression of RAS, inflammation, and oxidative stress in C57BL/6 mice fed a high-fat (HF) diet. The animals were fed a standard diet (10% fat, control), 60% fat (HF), HF + ASE (300 mg/kg per day) and HF + ENA (enalapril, 30 mg/kg per day) for 12 weeks. ASE and ENA prevented weight gain and adiposity, adipocyte hypertrophy, dyslipidemia, and insulin resistance. In adipose tissue, ASE increased the insulin receptor expression and reduced renin and AT1 receptor expression, which was associated with decreased plasma levels of renin and angiotensin II. Differently, ENA increased the expression of angiotensin-conversing enzyme 2, AT2, B2, and Mas receptors in adipose tissue. Also, ASE but not ENA decreased malondialdehyde and 8-isoprostane levels in adipose tissue. Finally, ASE and ENA reduced the adipose tissue inflammatory markers tumor necrosis factor alpha and interleukin 6. These results demonstrate that ASE prevented the adipocyte hypertrophy, obesity, hyperlipidemia, hyperglycemia, and insulin resistance in HF diet–fed mice. The downregulation of RAS in adipose tissue, reducing oxidative stress and inflammation, may contribute to the prevention of obesity-related disorders.     

Effect of Ethyl Pyruvate on Skeletal Muscle Metabolism in Rats Fed on a High Fat Diet

Impaired mitochondrial capacity may be implicated in the pathology of chronic metabolic diseases. To elucidate the effect of ethyl pyruvate supplementation on skeletal muscles metabolism we examined changes in activities of mitochondrial and antioxidant enzymes, as well as sulfhydryl groups oxidation (an indirect marker of oxidative stress) during the development of obesity. After 6 weeks feeding of control or high fat diet, Wistar rats were divided into four groups: control diet, control diet and ethyl pyruvate, high fat diet, and high fat diet and ethyl pyruvate. Ethyl pyruvate was administered as 0.3% solution in drinking water, for the following 6 weeks. High fat diet feeding induced the increase of activities 3-hydroxyacylCoA dehydrogenase, citrate synthase, and fumarase. Moreover, higher catalase and superoxide dismutase activities, as well as sulfhydryl groups oxidation, were noted. Ethyl pyruvate supplementation did not affect the mitochondrial enzymes’ activities, but induced superoxide dismutase activity and sulfhydryl groups oxidation. All of the changes were observed in soleus muscle, but not in extensor digitorum longus muscle. Additionally, positive correlations between fasting blood insulin concentration and activities of catalase (p = 0.04), and superoxide dismutase (p = 0.01) in soleus muscle were noticed. Prolonged ethyl pyruvate consumption elevated insulin concentration, which may cause modifications in oxidative type skeletal muscles.     

Subsarcolemmal and intermyofibrillar mitochondrial responses to short-term high-fat feeding in rat skeletal muscle

ObjectivesWe assessed the alterations in mitochondrial function in skeletal muscle that were elicited by short-term high-fat feeding in sedentary rats.MethodsTwo groups of rats were pair-fed for 1 wk and received a low-fat or high-fat diet. Body composition, energy balance, and glucose homeostasis were measured. Mitochondrial mass, oxidative capacity, and energetic efficiency as well as parameters of oxidative stress and antioxidant defense were evaluated in subsarcolemmal and intermyofibrillar mitochondria from the skeletal muscle.ResultsBody energy, lipid content, and metabolic efficiency were significantly higher and energy expenditure was significantly decreased among rats that were fed a high-fat diet, as compared with controls. Skeletal muscle mitochondrial energetic efficiency, oxidative capacity for lipid substrates, and antioxidant defense were significantly increased in rats that were fed a high-fat diet as compared with controls.ConclusionsAcute isocaloric high-fat feeding is able to induce increased phosphorylation efficiency in skeletal muscle subsarcolemmal and intermyofibrillar mitochondria. This modification implies a reduced oxidation of energy substrates that may contribute to the early onset of obesity.     

Inhibitory effects of Doenjang,Korean traditional fermented soybean paste,on oxidative stress and inflammation in adipose tissue of mice fed a high-fat diet

BACKGROUND/OBJECTIVES

Doenjang, Korean traditional fermented soybean paste has been reported to have an anti-obesity effect. Because adipose tissue is considered a major source of inflammatory signals, we investigated the protective effects of Doenjang and steamed soybean on oxidative stress and inflammation in adipose tissue of diet-induced obese mice.

MATERIALS/METHODS

Male C57BL/6J mice were fed a low fat diet (LF), a high-fat diet (HF), or a high-fat containing Doenjang diet (DJ) or a high-fat containing steamed soybean diet (SS) for 11 weeks.

RESULTS

Mice fed a DJ diet showed significantly lower body and adipose tissue weights than those in the HF group. Although no significant differences in adipocyte size and number were observed among the HF diet-fed groups, consumption of Doenjang alleviated the incidence of crown-like structures in adipose tissue. Consistently, we observed significantly reduced mRNA levels of oxidative stress markers (heme oxygenase-1 and p40^phox), pro-inflammatory adipokines (tumor necrosis factor alpha and macrophage chemoattractant protein-1), macrophage markers (CD68 and CD11c), and a fibrosis marker (transforming growth factor beta 1) by Doenjang consumption. Gene expression of anti-inflammatory adipokine, adiponectin was significantly induced in the DJ group and the SS group compared to the HF group. The anti-oxidative stress and anti-inflammatory effects observed in mice fed an SS diet were not as effective as those in mice fed a DJ diet, suggesting that the bioactive compounds produced during fermentation and aging may be involved in the observed health-beneficial effects of Doenjang.

CONCLUSIONS

Doenjang alleviated oxidative stress and restored the dysregulated expression of adipokine genes caused by excess adiposity. Therefore, Doenjang may ameliorate systemic inflammation and oxidative stress in obesity via inhibition of inflammatory signals of adipose tissue.     

Platycodon grandiflorum root attenuates vascular endothelial cell injury by oxidized low-density lipoprotein and prevents high-fat diet–induced dyslipidemia in mice by up-regulating antioxidant proteins

We hypothesized that a Platycodon grandiflorum root (PG) ethyl acetate extract (PGEA) would help reduce the vascular cell injury caused by oxidized low-density lipoprotein (oxLDL) and prevent high-fat (HF) diet–induced dyslipidemia and oxidative stress by up-regulating antioxidant proteins. We investigated the protective effects of PGEA against vascular endothelial cell injury induced by oxLDL and dyslipidemia induced by an HF diet, and the mechanisms underlying these effects were studied. The protective effects of PGEA were investigated with respect to calf pulmonary arterial endothelial (CPAE) cell viability and the lactate dehydrogenase release during oxLDL treatment. The in vivo effects of PGEA were examined using C57BL/6 mice, which were fed an HF diet for 9 weeks. The HF diet was supplemented with 0, 25, or 75 mg/kg PGEA during the last 4 weeks of the experimental period. Histologic analyses of hepatic lipid accumulation were performed. The changes in antioxidant protein levels induced by PGEA, which protects against HF diet–induced oxidative stress, were measured using a proteomics approach. We found that PGEA exhibited antioxidant activity. In CPAE cells, PGEA inhibited both oxLDL-induced cell death and lactate dehydrogenase release. In the HF diet–induced obese mice that received PGEA, we observed significantly reduced plasma and hepatic lipid levels, demonstrating that PGEA has beneficial effects on hyperlipidemia. In addition, we found that PGEA caused the up-regulation of antioxidant proteins. These findings suggest that the antioxidant effects of PGEA may protect against oxidative stress-related diseases.     

A high fat diet inhibits delta-aminolevulinate dehydratase and increases lipid peroxidation in mice (Mus musculus)

The aim of this study was examine the effects of high starch (HS) vs. high fat (HF) feeding on blood glycated hemoglobin (GHbA(1c)) level, thiobarbituric acid-reactive species (TBA-RS) concentration and delta-aminolevulinate dehydratase (delta-ALA-D) activity in mice. The GHbA(1c) level was significantly higher in mice fed the HF diet compared with those fed the HS diet. Hepatic, renal, and cerebral TBA-RS concentrations in mice fed the HF diet were significantly greater than in mice fed the HS diet. In addition, positive correlations were found between the GHbA(1c) and TBA-RS levels for hepatic (P < 0.05; r = 0.46), renal (P < 0.003; r = 0.65), and cerebral (P < 0.001; r = 0.69) tissues. The delta-ALA-D hepatic, renal and cerebral activities of mice fed the HF diet were significantly lower than those of mice fed the HS diet. Furthermore, a negative correlation was found between the GHbA(1c) level and delta-ALA-D activity in hepatic (P < 0.001; r = -0.77), renal (P < 0.007; r = -0.60), and cerebral (P < 0.007; r = -0.60) tissues. The results of this study indicate that consumption of a high fat diet promotes oxidative stress related to hyperglycemia, which in turn can stimulate glycation of proteins leading to delta-ALA-D inhibition in mice.     

Supplementation with Vitis vinifera L. skin extract improves insulin resistance and prevents hepatic lipid accumulation and steatosis in high-fat diet–fed mice

Nonalcoholic fatty liver disease is one of the most common complications of obesity. The Vitis vinifera L. grape skin extract (ACH09) is an important source of polyphenols, which are related to its antioxidant and antihyperglycemic activities. We hypothesized that ACH09 could also exert beneficial effects on metabolic disorders associated with obesity and evaluated ACH09’s influence on high-fat (HF) diet–induced hepatic steatosis and insulin resistance in C57BL/6 mice. The animals were fed a standard diet (10% fat, control) or an HF diet (60% fat, HF) with or without ACH09 (200 mg/[kg d]) for 12 weeks. Our results showed that ACH09 reduced HF diet–induced body weight gain, prevented hepatic lipid accumulation and steatosis, and improved hyperglycemia and insulin resistance. The underlying mechanisms of these beneficial effects of ACH09 may involve the activation of hepatic insulin-signaling pathway because the expression of phosphorylated insulin receptor substrate-1, phosphatidylinositol 3-kinase, phosphorylated Akt serine/threonine kinase 1, and glucose transporter 2 was increased by ACH09 and correlated with improvement of hyperglycemia, hyperinsulinemia, and insulin resistance. ACH09 reduced the expression of the lipogenic factor sterol regulatory-element binding protein-1c in the liver and upregulated the lipolytic pathway (phosphorylated liver kinase B1/phosphorylated adenosine-monophosphate–activated protein kinase), which was associated with normal hepatic levels of triglyceride and cholesterol and prevention of steatosis. ACH09 prevented the hepatic oxidative damage in HF diet–fed mice probably by restoration of antioxidant activity. In conclusion, ACH09 protected mice from HF diet–induced obesity, insulin resistance, and hepatic steatosis. The regulation of hepatic insulin signaling pathway, lipogenesis, and oxidative stress may contribute to ACH09’s protective effect.     

Resistance Exercise Training Improves Metabolic and Inflammatory Control in Adipose and Muscle Tissues in Mice Fed a High-Fat Diet

This study investigates whether ladder climbing (LC), as a model of resistance exercise, can reverse whole-body and skeletal muscle deleterious metabolic and inflammatory effects of high-fat (HF) diet-induced obesity in mice. To accomplish this, Swiss mice were fed for 17 weeks either standard chow (SC) or an HF diet and then randomly assigned to remain sedentary or to undergo 8 weeks of LC training with progressive increases in resistance weight. Prior to beginning the exercise intervention, HF-fed animals displayed a 47% increase in body weight (BW) and impaired ability to clear blood glucose during an insulin tolerance test (ITT) when compared to SC animals. However, 8 weeks of LC significantly reduced BW, adipocyte size, as well as glycemia under fasting and during the ITT in HF-fed rats. LC also increased the phosphorylation of Akt_Ser473 and AMPK_Thr172 and reduced tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL1-β) contents in the quadriceps muscles of HF-fed mice. Additionally, LC reduced the gene expression of inflammatory markers and attenuated HF-diet-induced NADPH oxidase subunit gp91phox in skeletal muscles. LC training was effective in reducing adiposity and the content of inflammatory mediators in skeletal muscle and improved whole-body glycemic control in mice fed an HF diet.     

Vitamin E protects against thyroxine-induced acceleration of lipid peroxidation in cardiac and skeletal muscles in rats

To determine whether vitamin E protects against thyroxine-induced oxidative stress in heart and soleus (slow oxidative) muscles, lipid peroxide (thiobarbituric acid-reactive substances) and antioxidant enzymes were measured in those tissues of hyperthyroid rats supplemented with vitamin E. The rats were rendered hyperthyroid by the administration of L-thyroxine in their drinking water. In experiment (EXPT) I, 30 mg/kg/dose of alpha-tocopheryl acetate was administered to the vitamin E-treated group. In EXPT II, the rats were fed a diet containing either less than 1 IU/kg (deficient diet), 20 IU/kg (control E diet), or 500 IU/kg (high E diet) of vitamin E and hyperthyroidism was induced. In EXPT I, hyperthyroidism induced an increase in oxidative enzymes, mitochondrial superoxide dismutase and lipid peroxide level, and a decrease in cytosolic superoxide dismutase, glutathione peroxidase and catalase in both tissues. Vitamin E treatment inhibited the increase in lipid peroxide level totally in the heart and partially in the soleus, with minimal changes in the other biochemical indices studied. In EXPT II, the lipid peroxide level was markedly increased in both tissues of the vitamin E-deficient group, and decreased in those of the group fed high E diet. There were some adaptive changes in the levels of cytosolic superoxide dismutase, glutathione peroxidase, and catalase in response to vitamin E deficiency, whereas neither oxidative enzymes nor mitochondrial superoxide dismutase were altered. These results suggest that vitamin E protects against lipid peroxidation in hyperthyroid heart and skeletal muscle independently of the changes in oxidative enzymes and antioxidant enzymes.     

Octanoic Acid-Enrichment Diet Improves Endurance Capacity and Reprograms Mitochondrial Biogenesis in Skeletal Muscle of Mice

Background: Medium Chain Fatty Acids (MCFAs) are a dietary supplement that exhibit interesting properties, due to their smaller molecular size. The acute consumption of MCFAs is expected to enhance exercise performance. However, the short-term effects of MCFAs on endurance performance remains poorly understood. The aim of our study is to evaluate the octanoic acid (C8)-rich diet effect on endurance capacity, and to explore their molecular and cellular effects. Methods: C57BL/6J mice were fed with a chow diet (Control group) or an octanoic acid-rich diet (C8 diet) for 6 weeks. Spontaneous activity, submaximal and maximal exercise tests were carried out to characterize the exercise capacities of the mice. Beta-oxidation and mitochondrial biogenesis pathways were explored in skeletal muscle by RT-qPCR, Western Blot (Quadriceps) and histochemical staining (Gastrocnemius). Results: Mice fed with a C8-rich diet presented a higher spontaneous activity (p < 0.05) and endurance capacities (p < 0.05) than the control, but no effect on maximal effort was observed. They also presented changes in the skeletal muscle metabolic phenotype, with a higher number of the oxidative fibers, rich in mitochondria. At the molecular level, the C8-diet induced an AMPK activation (p < 0.05), associated with a significant increase in PGC1a and CS gene expression and protein levels. Conclusion: Our study provided evidence that C8-enrichment as a food supplementation improves endurance capacities and activates mitochondrial biogenesis pathways leading to higher skeletal muscle oxidative capacities.     

Consumption of a high glycemic index diet increases abdominal adiposity but does not influence adipose tissue pro-oxidant and antioxidant gene expression in C57BL/6 mice

The hypothesis of this study is that consumption of a high glycemic index (GI) starch will increase adiposity, increase expression of the pro-oxidant enzyme (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase), and decrease expression of the antioxidant enzymes (catalase, glutathione peroxidase [GPx], and superoxide dismutase [SOD]) in adipose tissue of mice. C57BL/6 mice (n = 5-8/group) were fed a diet containing either high-GI starch (100% amylopectin) or low-GI starch (60% amylose/40% amylopectin) under low-fat (LF) or high-fat (HF) conditions for 16 weeks. Meal tolerance tests (MTTs) indicated that the postprandial blood glucose response over 120 minutes for the high-GI mice under LF and HF conditions was significantly greater than for mice fed low-GI diets. This result was not due to increased food consumption by the high-GI mice during the MTT. Although there was no difference in body weight between mice fed high-GI or low-GI starch, LF high-GI mice had significantly greater adiposity compared to LF low-GI mice. High-fat mice had a significant increase in NADPH oxidase expression compared to LF mice, but there was no significant effect of starch on NADPH oxidase expression. High-fat diet significantly decreased the expression of GPx and catalase, but there was no significant effect of starch on GPx and catalase expression. There was no difference in SOD expression among any of the diet groups. In conclusion, high GI diets increase adiposity under LF conditions but do not influence pro-oxidant or antioxidant enzyme gene expression in adipose tissue of C57BL/6 mice.     

Increased hepatic de novo lipogenesis and mitochondrial efficiency in a model of obesity induced by diets rich in fructose

Purpose

To assess hepatic de novo lipogenesis and mitochondrial energetics as well as whole-body energy homeostasis in sedentary rats fed a fructose-rich diet.

Methods

Male rats of 90 days of age were fed a high-fructose or control diet for 8 weeks. Body composition, energy balance, oxygen consumption, carbon dioxide production, non-protein respiratory quotient, de novo lipogenesis and insulin resistance were measured. Determination of specific activity of hepatic enzymes of de novo lipogenesis, mitochondrial mass, oxidative capacity and degree of coupling, together with parameters of oxidative stress and antioxidant defence, was also carried out.

Results

Body energy and lipid content as well as plasma insulin and non-esterified fatty acids were significantly higher in fructose-fed than in control rats. Significantly higher rates of net de novo lipogenesis and activities of hepatic lipogenic enzymes fatty acid synthase and stearoyl CoA desaturase-1 were found in fructose-fed rats compared to controls. Mitochondrial protein mass and degree of coupling were significantly higher in fructose-fed rats compared to controls. Hepatic mitochondria showed oxidative damage, both in the lipid and in the protein component, together with decreased activity of antioxidant defence.

Conclusion

Liver mitochondrial compartment is highly affected by fructose feeding. The increased mitochondrial efficiency allows liver cells to burn less substrates to produce ATP for de novo lipogenesis and gluconeogenesis. In addition, increased lipogenesis gives rise to whole body and ectopic lipid deposition, and higher mitochondrial coupling causes mitochondrial oxidative stress.     

Regulation of manganese superoxide dismutase (MnSOD) in chronic experimental alcoholism: effects of vitamin E-supplemented and -deficient diets

In order to investigate the pathogenic mechanism responsible for liver injury associated with chronic alcoholism, we studied the effects of different dietary vitamin E levels in chronically ethanol (EtOH)-fed rats on the activity and mRNA regulation of the manganese superoxide dismutase (MnSOD) enzyme. Evidence is accumulating that intermediates of oxygen reduction may in fact be associated with the development of alcoholic liver disease. Since low vitamin E liver content seems to potentiate EtOH-linked oxidative stress, we studied the effect of EtOH treatment in livers from rats fed a diet deficient or supplemented with vitamin E. Chronic EtOH feeding enhanced hepatic consumption of vitamin E in both groups of EtOH-treated animals, irrespectively of the vitamin E level of the basal diet and the effect was observed in both the microsomal and mitochondrial fractions. Both EtOH-fed groups exhibited increased MnSOD gene expression, while the enzyme activity was enhanced only in the vitamin E-deprived group of EtOH-treated animals. The significant increase in manganese liver content found only in this last group could explain the rise of enzyme activity. In fact, in the absence of a parallel increase of the prosthetic ion manganese, MnSOD mRNA induction was not accompanied by a higher enzymatic activity. These findings support the role of oxidative alteration in the EtOH-induced chronic hepatotoxicity in which MnSOD response might represent a primary defence mechanism against the damaging effect of oxygen radical species.     

Hepatic oxidative stress in fructose-induced fatty liver is not caused by sulfur amino acid insufficiency

Fructose-sweetened liquid consumption is associated with fatty liver and oxidative stress. In rodent models of fructose-mediated fatty liver, protein consumption is decreased. Additionally, decreased sulfur amino acid intake is known to cause oxidative stress. Studies were designed to test whether oxidative stress in fructose-sweetened liquid-induced fatty liver is caused by decreased ad libitum solid food intake with associated inadequate sulfur amino acid intake. C57BL6 mice were grouped as: control (ad libitum water), fructose (ad libitum 30% fructose-sweetened liquid), glucose (ad libitum 30% glucose-sweetened water) and pair-fed (ad libitum water and sulfur amino acid intake same as the fructose group). Hepatic and plasma thiol-disulfide antioxidant status were analyzed after five weeks. Fructose- and glucose-fed mice developed fatty liver. The mitochondrial antioxidant protein, thioredoxin-2, displayed decreased abundance in the liver of fructose and glucose-fed mice compared to controls. Glutathione/glutathione disulfide redox potential (E(h)GSSG) and abundance of the cytoplasmic antioxidant protein, peroxiredoxin-2, were similar among groups. We conclude that both fructose and glucose-sweetened liquid consumption results in fatty liver and upregulated thioredoxin-2 expression, consistent with mitochondrial oxidative stress; however, inadequate sulfur amino acid intake was not the cause of this oxidative stress.