Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that consumption of CLA and EPA alters lipid metabolism. CLA contains conjugated double bonds, and EPA is an n-3 PUFA. Based on the possibility that a molecule with both of these structures might have interesting physiological effects, we prepared conjugated FA from EPA by alkaline isomerization and examined the effects of the conjugated EPA (CEPA) on lipid metabolism in rats. Rats were fed by oral gavage every day for 4 wk with 200 mg of FA including linoleic acid, EPA, CLA, or CEPA. Compared with other groups, rats fed CEPA showed a significant weight loss in epididymal adipose tissue and significant decreases in the levels of liver TAG and total cholesterol (TC), indicating reduced accumulation of lipid in the liver and adipose tissue. The plasma levels of TAG, TC, FFA, and tumor necrosis factor-alpha in rats fed CEPA were reduced, as was the activity of the FA synthesis system in the liver, whereas the FA-beta-oxidation system was activated by CEPA. These results suggest that intake of CEPA suppresses lipid accumulation in the liver and epididymal adipose tissue while increasing lipid catabolism in rats.
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PMID:Intake of conjugated eicosapentaenoic acid suppresses lipid accumulation in liver and epididymal adipose tissue in rats. 1645 23

Fenofibrate, a selective (1)PPAR-alpha activator, is prescribed to treat human dyslipidemia. The aim of this study was to delineate the mechanism of fenofibrate-mediated reductions in adiposity, improvements in insulin sensitivity, and lowering of triglycerides (TG) and free fatty acids (FFA) and to investigate if these favorable changes are related to the inhibition of lipid deposition in the aorta. To test this hypothesis we used male LDLr deficient mice that exhibit the clinical features of metabolic syndrome X when fed a high fat high cholesterol (HF) diet. LDLr deficient mice fed HF diet and simultaneously treated with fenofibrate (100 mg/kg body weight) prevented development of obesity, lowered serum triglycerides and cholesterol, improved insulin sensitivity, and prevented accumulation of lipids in the aorta. Lowering of circulating lipids occurred via down-regulation of lipogenic genes, including fatty acid synthase, acetyl CoA carboxylase and diacyl glycerol acyl transferase-2, concomitant with decreased liver TG and cholesterol, and TG output rate. Fenofibrate also suppressed liver apoCIII mRNA levels and markedly increased lipoprotein lipase mRNA levels, known to enhance serum TG catabolism. In addition, fenofibrate profoundly reduced epididymal fat and mesenteric fat mass to the levels seen in lean mice. The reductions in body weight were associated with elevation of hepatic uncoupling protein 2 (UCP2) mRNA, a concomitant increase in the ketone body formation, and improved insulin sensitivity associated with tumor necrosis factor-alpha reductions and phosphoenol pyruvate carboxykinase down-regulation. These results demonstrate that fenofibrate improves lipid abnormalities partly via inhibition of TG production and partly via clearance of TG-rich apoB particles by elevating LPL and reduced apoCIII. The prevention of obesity development occurred via energy expenditure. Fenofibrate-mediated hypolipidemic effects together with improved insulin sensitivity and loss of adiposity led to the reductions in the aortic lipid deposition by inhibiting early stages of atherosclerosis possibly via vascular cell adhesion molecule-1 (VCAM-1) modulation. These results suggest that potent PPAR-alpha activators may be useful in the treatment of syndrome X.
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PMID:Peroxisome proliferator-activated receptor-alpha selective ligand reduces adiposity, improves insulin sensitivity and inhibits atherosclerosis in LDL receptor-deficient mice. 1647 80

Crocetin, a unique carotenoid with potent antioxidative and anti-inflammatory activities, is a major ingredient of saffron which is used as an important spice and food colorant in various parts of the world. In the present study, the effect of crocetin on insulin resistance and its related abnormalities induced by high-fructose diet were investigated in male Wistar rats. Compared to the control rats fed on normal laboratory diet, fructose-fed rats developed a series of pathological changes including insulin resistance, hyperinsulinemia, dyslipidemia and hypertension. Although having no evident effect on the body weight, fructose feeding caused a marked increase in the weight of epididymal white adipose tissue. Furthermore, a significant reduction in the expression of both protein and mRNA of adiponectin (an insulin-sensitizing adipocytokine) was observed, whereas those of tumor necrosis factor (TNF)-alpha and leptin were enhanced in epididymal white adipose tissue in fructose-fed rats. These disorders were effectively normalized in crocetin-treated rats. Crocetin was also demonstrated here to alleviate free fatty acid (FFA)-induced insulin insensitivity and dysregulated mRNA expression of adiponectin, TNF-alpha and leptin in primary cultured rat adipocytes. These findings suggest the possibility of crocetin treatment as a preventive strategy of insulin resistance and related diseases. The favorable impact on adiponectin, TNF-alpha and leptin expression in white adipose tissue may be involved in the improvement of insulin sensitivity observed in crocetin-treated rats.
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PMID:Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructose-fed rats. 1671 30

Recently, the insulin-sensitizing adipokine adiponectin and the insulin resistance-inducing adipokine tumor necrosis factor-alpha (TNF-alpha) were reported to inhibit each other's production in adipocytes. We investigated the effects of two beta(3)-adrenoceptor agonists, 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316,243) and (+/-)-(R(*),R(*))-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid (BRL37344), on the gene expression of adiponectin, two adiponectin receptors, and TNF-alpha in adipose tissues of C57BL/6J mice. CL-316,243 and BRL37344 downregulated adiponectin, but upregulated adiponectin receptor 2 (not receptor 1) in epididymal or/and subcutaneous white adipose tissues and in brown adipose tissue. TNF-alpha expression was upregulated only in epididymal adipose tissue. To further explore these effects, we treated differentiated 3T3-L1 adipocytes with the non-selective beta-adrenoceptor agonist isoproterenol. As a result, adiponectin receptor 2 (but not receptor 1) gene expression and TNF-alpha protein expression increased, but gene expression and secretion of adiponectin decreased. The upregulation of adiponectin receptor 2 by isoproterenol is most likely via beta(2),beta(3)-adrenoceptors, adenylyl cyclases, and protein kinase A (PKA). However, the accompanying activation of AMP-activated protein kinase (AMPK) may inhibit this upregulation. Our results suggest that upregulation of TNF-alpha and downregulation of adiponectin by beta-adrenoceptor activation may contribute to the pathogenesis of catecholamine-induced insulin resistance, and that upregulation of adiponectin receptor 2 may be a feedback result of reduced adiponectin.
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PMID:beta-adrenoceptor agonists downregulate adiponectin, but upregulate adiponectin receptor 2 and tumor necrosis factor-alpha expression in adipocytes. 1757 33

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

We investigated the effects of beta(3)-adrenoceptor agonist, 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316,243) in obese diabetic KKAy mice. Two weeks' subcutaneous administration of CL-316,243 reduced serum levels of glucose, insulin, triglyceride, free fatty acid and tumor necrosis factor-alpha (TNF-alpha), and increased adiponectin. Adiponectin, adiponectin receptors and beta(3)-adrenoceptor mRNA expressions were reduced in epididymal white adipose tissue in KKAy mice, and CL-316,243 recovered these mRNA expressions. Meanwhile, CL-316,243 suppressed the overexpressed mRNA level of TNF-alpha in both epididymal white adipose tissue and brown adipose tissue. These data suggest that the normalization of adiponectin, adiponectin receptors and TNF-alpha may result in the amelioration of obesity-induced insulin resistance.
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PMID:The effects of beta(3)-adrenoceptor agonist CL-316,243 on adiponectin, adiponectin receptors and tumor necrosis factor-alpha expressions in adipose tissues of obese diabetic KKAy mice. 1830 29

Toll-like receptor-4 (Tlr-4), a key pattern recognition receptor involved in innate immune response, is activated by saturated fatty acids (SFAs). To investigate the involvement of this receptor in obesity caused by consumption of diets high in fat, we utilized male Tlr-4-deficient 10ScN mice and 10J controls. Mice were fed either low fat (low-fat control (LFC)), high unsaturated fat (high-fat control (HFC)), or high saturated fat + palmitate (HFP) diets ad libitum for 16 weeks. Relative to the LFC diet, the HFC diet resulted in greater epididymal fat pad weights and adipocyte hypertrophy in both Tlr-4-deficient and normal mice. However, the 10ScN mice were completely protected against the obesigenic effects of the HFP diet. Moreover, macrophage infiltration and monocyte chemotactic protein-1 (MCP-1) transcript abundance were lower in adipose tissue of 10ScN mice fed the HFP diet, and the hyperinsulinemic response was negated. Tlr-4-deficient mice also had markedly lower circulating concentrations of MCP-1 and much less nuclear factor-kappaB (NFkappaB) protein in nuclear extracts prepared from adipose tissue, irrespective of diet. In contrast, Tlr-4 deficiency did not attenuate the induction of tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6) expression in adipose tissue. These data indicate that Tlr-4 deficiency selectively protects against the obesigenic effects of SFA and alters obesity-related inflammatory responses in adipose tissue.
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PMID:Tlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat. 1842 Dec 79

Dermcidin (DCD), an antimicrobial peptide that is secreted by sweat glands, is reportedly a human homolog of mouse proteolysis-inducing factor. This study was conducted to investigate the effect of DCD on body fat mobilization. The expression level of DCD in the livers of Ad-DCD-injected mice was higher than in those of Ad-beta-galactosidase (Ad-beta-gal)-injected mice 7 days after injection. In addition, injection with the Ad-DCD virus led to decreased body weight and epididymal fat mass when compared with controls. The plasma triglyceride level was decreased, whereas the free fatty acid and glycerol levels were increased in the Ad-DCD-injected group. Epididymal adipose tissues obtained from Ad-DCD-injected mice consisted of smaller adipocytes than tissues obtained from Ad-beta-gal-injected mice. The gene expression profiles revealed an upregulation of hormone-sensitive lipase and adipose fatty acid-binding protein, both of which are involved in adipocyte lipolysis, in Ad-DCD-injected mice, and this lipolytic effect of DCD paralleled the increase of circulating tumor necrosis factor-alpha (TNF-alpha) level that was observed. The perilipin levels in adipose tissue were decreased in Ad-DCD-injected mice when compared with those of the control mice. Taken together, these results suggest that DCD-mediated body fat reduction might occur as a result of TNF-alpha-induced downregulation of perilipin in adipose tissue.
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PMID:Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice. 1846 79

The aim of the present study was to investigate the anti-obesity effect of a mixture composed of Garcinia cambogia extract, soypeptide, and L: -carnitine (1.2:0.3:0.02, w/w/w) in rats rendered obese by a high-fat diet (HFD). Sprague-Dawley rats were fed either the high-fat control diet (CD) or the 0.38% mixture-supplemented HFD (CD + M) for 9 weeks. The mixture significantly reduced body weight gain and the accumulation of visceral fat mass in a rat model of HFD-induced obesity. Moreover, the mixture effectively lowered blood and hepatic lipid concentrations and serum glucose, insulin, c-peptide, and leptin levels in rats with HFD-induced obesity. Results from real-time reverse transcription-polymerase chain reaction analyses indicated that the expression levels of leptin, tumor necrosis factor-alpha (TNF-alpha), and sterol regulatory element binding protein 1c (SREBP1c) genes in the epididymal fat tissue of rats fed the CD + M diet were 0.4-, 0.6-, and 0.48-fold, respectively, of those found in the CD rats (P < 0.05), while expression of the uncoupling protein 2 (UCP2) gene in epididymal adipose tissue was 1.25-fold (P < 0.05) of that found in CD rats. In conclusion, a mixture composed of G. cambogia extract, soy peptide, and L: -carnitine attenuated visceral fat accumulation and improved dyslipidemia in a rat model with HFD-induced obesity.
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PMID:A mixture of the aqueous extract of Garcinia cambogia, soy peptide and L: -carnitine reduces the accumulation of visceral fat mass in rats rendered obese by a high fat diet. 1885 Feb 30

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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