Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary fish oil rich in (n-3) fatty acids plays an important role in reducing abnormalities associated with the metabolic syndrome and mortality from coronary heart disease. We investigated the effects of dietary fish oil on the metabolic syndrome in a high-sucrose-fed rat model. The model was achieved by the administration of 30% sucrose in drinking water in male Wistar rats during 21 weeks. After the metabolic syndrome rat model was established, fish oil was administered during 6 weeks. The metabolic syndrome rats showed significant increases in body weight, systolic blood pressure, serum insulin, total lipids, triacylglycerols, cholesterol, free fatty acids, LDL, total proteins, albumin, and serum tumor necrosis factor-alpha (TNF-alpha). They also presented abdominal and epididymal fat accumulation and fatty liver. After fish oil diet administration, metabolic syndrome rats had a significant reduction in blood pressure, serum insulin, triacylglycerols, cholesterol, free fatty acids, and total lipids, but no change was observed in TNF-alpha concentration or fat accumulation. In conclusion, fish oil reversed the alterations on metabolic parameters and blood pressure exerted by sucrose administration, although it had no effect on TNF-alpha production and adiposity. This confirms the theory that the molecular etiology of the metabolic syndrome is multifactorial, as is the effect of n-3 polyunsaturated fatty acids (PUFAs) upon it, having complex and multifaceted actions.
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PMID:Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor-alpha in rats with sucrose-induced metabolic syndrome. 1515 41

NADPH is an essential cofactor for many enzymatic reactions including glutathione metabolism and fat and cholesterol biosynthesis. We have reported recently an important role for mitochondrial NADP(+)-dependent isocitrate dehydrogenase in cellular defense against oxidative damage by providing NADPH needed for the regeneration of reduced glutathione. However, the role of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is still unclear. We report here for the first time that IDPc plays a critical role in fat and cholesterol biosynthesis. During differentiation of 3T3-L1 adipocytes, both IDPc enzyme activity and its protein content were increased in parallel in a time-dependent manner. Increased expression of IDPc by stable transfection of IDPc cDNA positively correlated with adipogenesis of 3T3-L1 cells, whereas decreased IDPc expression by an antisense IDPc vector retarded adipogenesis. Furthermore, transgenic mice with overexpressed IDPc exhibited fatty liver, hyperlipidemia, and obesity. In the epididymal fat pads of the transgenic mice, the expressions of adipocyte-specific genes including peroxisome proliferator-activated receptor gamma were markedly elevated. The hepatic and epididymal fat pad contents of acetyl-CoA and malonyl-CoA in the transgenic mice were significantly lower, whereas the total triglyceride and cholesterol contents were markedly higher in the liver and serum of transgenic mice compared with those measured in wild type mice, suggesting that the consumption rate of those lipogenic precursors needed for fat biosynthesis must be increased by elevated IDPc activity. Taken together, our findings strongly indicate that IDPc would be a major NADPH producer required for fat and cholesterol synthesis.
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PMID:Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism. 1525 34

Raspberry ketone (4-(4-hydroxyphenyl) butan-2-one; RK) is a major aromatic compound of red raspberry (Rubus idaeus). The structure of RK is similar to the structures of capsaicin and synephrine, compounds known to exert anti-obese actions and alter the lipid metabolism. The present study was performed to clarify whether RK helps prevent obesity and activate lipid metabolism in rodents. To test the effect on obesity, our group designed the following in vivo experiments: 1) mice were fed a high-fat diet including 0.5, 1, or 2% of RK for 10 weeks; 2) mice were given a high-fat diet for 6 weeks and subsequently fed the same high-fat diet containing 1% RK for the next 5 weeks. RK prevented the high-fat-diet-induced elevations in body weight and the weights of the liver and visceral adipose tissues (epididymal, retroperitoneal, and mesenteric). RK also decreased these weights and hepatic triacylglycerol content after they had been increased by a high-fat diet. RK significantly increased norepinephrine-induced lipolysis associated with the translocation of hormone-sensitive lipase from the cytosol to lipid droplets in rat epididymal fat cells. In conclusion, RK prevents and improves obesity and fatty liver. These effects appear to stem from the action of RK in altering the lipid metabolism, or more specifically, in increasing norepinephrine-induced lipolysis in white adipocytes.
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PMID:Anti-obese action of raspberry ketone. 1586 4

Many previous studies have reported that conjugated linoleic acid could be produced by starter culture bacteria, but the effects of the bacteria were not investigated. Moreover, there was no evidence of the conjugated linoleic acid-producing bacteria having potential health or nutritional effects related to conjugated linoleic acid, including reducing body fat. Here, we investigated the anti-obesity effect of Lactobacillus rhamnosus PL60, a human originated bacterium that produces t10, c12-conjugated linoleic acid, on diet-induced obese mice. After 8 weeks of feeding, L. rhamnosus PL60 reduced body weight without reducing energy intake, and caused a significant, specific reduction of white adipose tissue (epididymal and perirenal). Although the size of epididymal adipocytes was not reduced by L. rhamnosus PL60, apoptotic signals and UCP-2 mRNA levels increased in adipose tissue. Liver steatosis, a well known side effect of CLA, was not observed by L. rhamnosus PL60 treatment; on the contrary it seemed to be normalized. Results showed that the amount of conjugated linoleic acid produced by Lactobacillus rhamnosus PL60 was enough to produce an anti-obesity effect.
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PMID:Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. 1680 88

Casein-based diets containing a low (LDI) or high (HDI) dose of soya protein concentrate enriched with isoflavones were fed to obese Zucker rats for 6 weeks. HDI feeding, but not LDI feeding, reduced the fatty liver and decreased the plasma levels of alanine transaminase and aspartate transaminase. This was accompanied by increased activities of mitochondrial and peroxisomal beta-oxidation, acetyl-CoA carboxylase, fatty acid synthase and glycerol-3-phosphate acyltransferase in liver and increased triacylglycerol level in plasma. The decreased fatty liver and the increased plasma triacylglycerol level appeared not to be caused by an increased secretion of VLDL, as HDI decreased the hepatic mRNA levels of apo B and arylacetamide deacetylase. However, the gene expression of VLDL receptor was markedly decreased in liver, but unchanged in epididymal white adipose tissue and skeletal muscle of rats fed HDI, indicating that the liver may be the key organ for the reduced clearance of triacylglycerol-rich lipoproteins from plasma after HDI feeding. The n-3/n-6, 20:4n-6/18:2n-6 and (20:5n-3+22:6n-3)/18:3n-3 ratios were increased in liver triacylglycerol by HDI. The phospholipids in liver of rats fed HDI contained a low level of 20:4n-6 and a high level of 20:5n-3, favouring the production of anti-inflammatory eicosanoids. When obese Zucker rats were fed soya protein, this also resulted in reduced fatty liver, possibly through reduced clearance of VLDL by the liver. We conclude that the isoflavone-enriched soya concentrate as well as soya protein may be promising dietary supplements for treatment of non-alcoholic fatty liver.
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PMID:Dietary soya protein concentrate enriched with isoflavones reduced fatty liver, increased hepatic fatty acid oxidation and decreased the hepatic mRNA level of VLDL receptor in obese Zucker rats. 1692 18

Conjugated linoleic acid (CLA) causes insulin resistance and hepatic steatosis in conjunction with depletion of adipokines in some rodent models. Our objective was to determine whether the maintenance of adipokines, mainly leptin and adiponectin, by either removing CLA from diets or using an adiponectin enhancer, rosiglitazone (ROSI), could attenuate CLA-induced insulin resistance. Male C57BL/6 mice were consecutively fed two experimental diets containing 1.5% CLA mixed isomer for 4 weeks followed by a diet without CLA for 4 weeks. CLA significantly depleted adiponectin but not leptin and was accompanied by hepatic steatosis and insulin resistance. These effects were attenuated after switching mice to the diet without CLA along with restoration of adiponectin. To further elucidate the role of adiponectin in CLA-mediated insulin resistance, ROSI was used in a subsequent study in male ob/ob mice fed either control (CON) or CLA diet. ROSI maintained significantly higher adiponectin levels in CON- and CLA-fed mice and prevented the depletion of epididymal adipose tissue and the development of insulin resistance. In conclusion, we show that insulin resistance induced by CLA may be related more to adiponectin depletion than to leptin and that maintaining adiponectin levels alone either by removing CLA or using ROSI can attenuate these effects.
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PMID:Maintenance of adiponectin attenuates insulin resistance induced by dietary conjugated linoleic acid in mice. 1705 Sep 6

Dysfunctional cross talk between adipose tissue and liver tissue results in metabolic and inflammatory disorders. As an insulin sensitizer, rosiglitazone (Rosi) improves insulin resistance yet causes increased adipose mass and weight gain in mice and humans. Conjugated linoleic acid (CLA) reduces adipose mass and body weight gain but induces hepatic steatosis in mice. We examined the combined effects of Rosi and CLA on adiposity, insulin sensitivity, and hepatic steatosis in high-fat-fed male C57Bl/6 mice. CLA alone suppressed weight gain and adipose mass but caused hepatic steatosis. Addition of Rosi attenuated CLA-induced insulin resistance and dysregulation of adipocytokines. In adipose, CLA significantly suppressed lipoprotein lipase and fatty acid translocase (FAT/CD36) mRNA, suggesting inhibition of fatty acid uptake into adipose; addition of Rosi completely rescued this effect. In addition, CLA alone increased markers of macrophage infiltration, F4/80, and CD68 mRNA levels, without inducing TNF-alpha in epididymal adipose tissue. The ratio of Bax to Bcl2, a marker of apoptosis, was significantly increased in adipose of the CLA-alone group and was partially prevented by treatment of Rosi. Immunohistochemistry of F4/80 demonstrates a proinflammatory response induced by CLA in epididymal adipose. In the liver, CLA alone induced microsteatotic liver but surprisingly increased the rate of very-low-density lipoprotein-triglyceride production without inducing inflammatory mediator-TNF-alpha and markers of macrophage infiltration. These changes were accompanied by significantly increased mRNA levels of stearoyl-CoA desaturase, FAT/CD36, and fatty acid synthase. The combined administration of CLA and Rosi reduced hepatic liver triglyceride content as well as lipogenic gene expression compared with CLA alone. In summary, dietary CLA prevented weight gain in Rosi-treated mice without attenuating the beneficial effects of Rosi on insulin sensitivity. Rosi ameliorated CLA-induced lipodystrophic disorders that occurred in parallel with rescued expression of adipocytokine and adipocytes-abundant genes.
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PMID:Combined effects of rosiglitazone and conjugated linoleic acid on adiposity, insulin sensitivity, and hepatic steatosis in high-fat-fed mice. 1732 64

Obesity is commonly associated with development of insulin resistance and systemic evidence of inflammation. Macrophages contribute to inflammatory amplification in obesity and may contribute directly to insulin resistance and the development of nonalcoholic fatty liver disease through the production of inflammatory cytokines, including tumor necrosis factor (TNF)-alpha. To test this hypothesis, we transplanted male wild-type (WT) and TNF-alpha deficient (KO) mice with either TNF-alpha-sufficient (TNF-alpha(+/+)) or TNF-alpha-deficient (TNF-alpha(-/-)) bone marrow. After consuming a high-fat diet for 26 wk, metabolic and morphometric characteristics of the animals were analyzed. While there were no differences in terms of relative weight gain, body composition analysis yielded a lower relative adipose and higher relative lean mass in mice lacking TNF-alpha, which was partially explained by reduced epididymal fat pad and liver weight. TNF-alpha(-/-) -->KO mice exhibited enhanced insulin sensitivity compared with that observed in TNF-alpha(+/+)-->KO mice; remarkably, no protection against insulin resistance was provided by transplanting TNF-alpha(-/-) bone marrow in WT mice compared with TNF-alpha(+/+)-->WT. The preserved insulin sensitivity seen in TNF-alpha(-/-)-->KO mice provided protection against the development of hepatic steatosis. Taken together, these data indicate that macrophage-derived TNF-alpha contributes to the pattern and extent of fat accumulation and insulin resistance in diet-induced obesity; however, this contribution is negligible in the presence of host-derived TNF-alpha.
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PMID:Macrophage TNF-alpha contributes to insulin resistance and hepatic steatosis in diet-induced obesity. 1757 85

The aim of present study was to identify the visceral adipose tissue genes differentially expressed in a well-characterized rat model of high-fat diet (HFD)-induced obesity. Male Sprague-Dawley rats were fed either the HFD (17 g lard + 3 g corn oil/100 g) or the normal diet (5 g corn oil/100 g) for 9 weeks. The HFD rats weighed 55% more and accumulated 85% to 133% greater visceral fats than did the normal-diet rats (P < .05). Animals given the HFD for 9 weeks acquired dyslipidemia, fatty liver, insulin resistance, and hyperleptinemia along with the overexpression of several obesity-related genes, such as leptin, tumor necrosis factor alpha, resistin, peroxisome proliferator-activated receptor gamma2, CCAAT/enhancer-binding protein alpha, and sterol regulatory element-binding protein-1c, in the epididymal adipose tissue. The differential gene expression profile obtained from the cDNA microarray analysis followed by the real-time polymerase chain reaction confirmation led to a recruitment of several uncharacterized adipose tissue genes responding to the HFD. We report herein, for the first time, that a series of genes which might be implicated in the insulin-stimulated glucose transporter 4 translocation, such as protein phosphatase 2 (formerly 2A), cell division cycle 42-interacting protein 4, syntaxin 6, linker of T-cell receptor pathways 10, as well as the genes which might be involved in cancer development, such as heat shock 10-kd protein 1, and ras-related C3 botulinum toxin substrate 1, were differentially expressed in the epididymal adipose tissue of rats rendered obese by an HFD.
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PMID:Genes are differentially expressed in the epididymal fat of rats rendered obese by a high-fat diet. 1908 40

The aim was to examine the role of cyclooxygenase (COX)-2-mediated inflammation in the development of obese linked insulin resistance and fatty liver. The rats were fed separately regular diet (CONT), high-fat diet (HFD) ad libitum, or energy restrictedly for 12 weeks. Rats fed HFD ad libitum were further divided into three subgroups co-treated with vehicle (HFa), or a selective COX-2 inhibitor celecoxib (HFa-Cel) or mesulid (HFa-Mes). Euglycemic hyperinsulinemic clamp (EHC) experiment was performed at the end of study. Another set of rats with similar grouping was further divided into those with a 4, 8, or 12-week intervention period for hepatic sampling. Body weight was increased significantly and similarly in HFa, HFa-Cel, and HFa-Mes. Time-dependent increases in plasma insulin, glucose, 8-isoprostanes, leptin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and hepatic triglyceride contents shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. During EHC period, the reduction in stimulation of whole body glucose uptake, suppression of hepatic glucose production and metabolic clearance rate of insulin shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The enhanced COX-2 and tumor necrosis factor-alpha (TNF-alpha) but attenuated PPAR-gamma and C/EBP-alpha mRNA expressions in epididymal fat shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The increases in average cell size of adipocytes and CD68 positive cells shown in HFa were also significantly reversed in HFa-Cel and HFa-Mes. Our findings suggest that COX-2 activation in fat inflammation is important in the development of insulin resistance and fatty liver in high fat induced obese rats.
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PMID:COX-2-mediated inflammation in fat is crucial for obesity-linked insulin resistance and fatty liver. 1924 74


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