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)

Macrophage migration inhibitory factor (MIF) has been rediscovered as a proinflammatory cytokine, pituitary hormone, and glucocorticoid-induced immunoregulator. A survey of tissue distribution revealed that MIF expression is not limited to T lymphocytes, but exists in several other tissues; however, its presence in adipose tissue has never been investigated. In this study, we examined the expression of MIF in adipose tissue using the rat epididymal fat pad and murine 3T3-L1 adipocytes. Northern and Western blot analyses revealed the expression of MIF mRNA and MIF protein, respectively, in both the fat pad and the adipocyte cell line. In immunohistochemistry, a positive staining reaction with an anti-rat MIF antibody was detected largely in the cytosol of adipocytes of the epididymal fat pad. To examine the production and release of MIF by adipocytes, we examined its content in the culture medium of the 3T3-L1 adipocytes. The results showed that MIF content was 1.6 +/- 0.48 ng/ml (mean +/- SD) after 24 hr culture, and the content was increased up to 9.7 +/- 2.8 ng/ml by stimulation with TNF-alpha (50 nM). Since TNF-alpha produced in adipocytes is known to induce insulin resistance, the results suggest the possibility that MIF plays an important role in the mechanism of insulin resistance often observed in obesity and diabetes via regulation of TNF-alpha expression.
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PMID:Identification of macrophage migration inhibitory factor in adipose tissue and its induction by tumor necrosis factor-alpha. 919 42

To address the hypothesis that tumor necrosis factor (TNF)-alpha has a role in obesity-associated insulin resistance or the regulation of in vivo lipid metabolism, mice with targeted disruption of the TNF-alpha gene were generated and studied. The absence of TNF-alpha protein in TNF-null (-/-) mice was confirmed. Lean or obese (gold-thioglucose [GTG]-injected) homozygous (-/-) mice were compared with lean or obese age- and sex-matched wild-type (+/+) mice derived from the same line at 13, 19, and 28 weeks of age. The following parameters were significantly affected in lean -/- versus +/+ mice: Body weight was not affected until week 28 (decreased by 14%); epididymal fat pad weight also decreased (25%) at this time, as did percentage body fat (16%), while percentage body protein was increased 13%. Fed plasma insulin levels decreased 47% (28 weeks), triglyceride levels decreased (all three ages; maximum 35% at 19 weeks), and fed plasma leptin decreased 33% (28 weeks). Fasting glucose was slightly (10%) reduced, but the glucose response to an oral glucose tolerance test (OGTT) was not affected. There was a trend (NS) toward increased total adipose tissue lipoprotein lipase in -/- versus +/+ mice. GTG-treatment resulted in obese -/- and +/+ mice with equal mean body weights (42 and 58% increased weight versus lean mice). The following parameters were significantly different in obese -/- mice: fasting plasma glucose decreased 13% (28 weeks), fed plasma insulin decreased 67% (28 weeks), and insulin response to OGTT was decreased by 50%. For both groups of obese mice, glucose levels during the OGTT were substantially increased compared with those in lean mice; however, mean stimulated glucose levels were 20% lower in obese -/- versus +/+ mice. We conclude 1) that TNF-alpha functions to regulate plasma triglycerides and body adiposity and 2) that although TNF-alpha contributes to reduced insulin sensitivity in older or obese mice, the absence of TNF-alpha is not sufficient to substantially protect against insulin resistance in the GTG hyperphagic model of rodent obesity.
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PMID:Targeted disruption of the tumor necrosis factor-alpha gene: metabolic consequences in obese and nonobese mice. 928 59

The relationship of leptin gene expression to adipocyte volume was investigated in lean 10-wk-old male C57BL/6J mice. mRNA levels for leptin, insulin receptor, glucocorticoid receptor, and tumor necrosis factor (TNF)-alpha in inguinal, epididymal, and retroperitoneal adipose tissues were quantified and related to adipocyte volume. Leptin mRNA levels were highly correlated with adipocyte volume within each fat depot. Multiple regression analysis of pooled data from the three depots showed that leptin mRNA levels were strongly correlated with adipocyte volumes (beta = 0.84, P < 0.001) and, to a smaller degree, with glucocorticoid receptor mRNA levels (beta = 0.36, P < 0.001). Depot of origin had no effect (P > 0.9). Rates of leptin secretion in vitro were strongly correlated with leptin mRNA levels (r = 0.89, P < 0.001). mRNA levels for TNF-alpha, insulin receptor, and glucocorticoid receptor showed no significant correlation with adipocyte volume. These results demonstrate that depot-specific differences in leptin gene expression are mainly related to the volumes of the constituent adipocytes. The strong correlation between leptin gene expression and adipocyte volume supports leptin's physiological role as a humoral signal of fat mass.
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PMID:Determinants of leptin gene expression in fat depots of lean mice. 1174 42

To study whether the body fat-reducing potential of conjugated linoleic acid (CLA) could be increased through dietary manipulations, the effects of the combination of CLA with different proteins, fats, and sesamin were examined in rats. Male rats were fed diets containing 1% CLA or linoleic acid (LA) in combination with different proteins (20% of casein or soybean protein), fats (7% perilla oil or soybean oil) and 0.2% sesamin (SES) for 3 or 4 weeks. When the dietary fat source was soybean oil, CLA, as compared with LA, significantly reduced weights of epididymal and perirenal adipose tissues, irrespective of the dietary protein sources. However, the highest reducing effect was shown when soybean protein was given as a protein source. SES stimulated the reduction of epididymal and perirenal adipose tissue weights in both protein diets. In contrast, CLA increased the weight of brown adipose tissue, and SES further increased it in combination with soybean oil but not with perilla oil. No effect of dietary manipulation was observed on serum leptin and TNF-alpha levels. Thus, the body fat-reducing potential of CLA can be increased by an appropriate combination with food factors that may stimulate fatty acid beta-oxidation.
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PMID:Dietary manipulations of body fat-reducing potential of conjugated linoleic acid in rats. 1179 29

Tumor necrosis factor (TNF)-alpha stimulates the secretion of the adipocyte-derived hormone leptin. However, the cellular mechanisms by which TNF-alpha influences leptin production are poorly understood. To examine this issue, epididymal fat pads were isolated from mice and cultured in recombinant murine TNF-alpha (100 ng/ml). Compared with medium-treated controls, steady-state leptin expression was increased in TNF-alpha-treated explants. Culture with inhibitors of translation (cycloheximide) or transcription (actinomycin-D) abrogated the induction of leptin following TNF-alpha. Explants were also cultured in the presence of the anti-inflammatory p38 mitogen-activated protein kinase inhibitor (SB-203580) or PG J(2) metabolite [15-deoxy-Delta(12,14)-PG J(2) (PGJ)] and then exposed to TNF-alpha. Both compounds completely abolished TNF-alpha-induced increases in leptin production. To test the relevance of this in vivo, mice were pretreated with PGJ and then given TNF-alpha. PGJ treatment markedly blunted the TNF-alpha-induced increase in leptin, TNF-alpha, and interleukin-6 gene expression in epididymal adipose tissue. Collectively, these data indicate that TNF-alpha acutely activates leptin expression and that anti-inflammatory agents can abrogate TNF-alpha-induced hyperleptinemia.
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PMID:Anti-inflammatory agents inhibit the induction of leptin by tumor necrosis factor-alpha. 1195 86

Because leptin stimulates nitric oxide (NO) release from the hypothalamus and anterior pituitary gland, we hypothesized that it also might release NO from adipocytes, the principal source of leptin. Consequently, plasma concentrations of leptin and NO, estimated from its metabolites NO(3) and NO(2) (NO(3)-NO(2)), were measured in adult male rats. There was a linear increase of both leptin and NO(3)-NO(2) with body weight that was associated with a parallel rise in fat mass. These findings indicate that release of leptin and NO is directly related to adipocyte mass. Furthermore, there was a parallelism in circadian rhythm of both substances, with peaks at 0130 h and nadirs at 0730 h. Measurement of both leptin and NO(3)-NO(2) in plasma from individual rats revealed that NO(3)-NO(2) increased linearly with leptin. Incubation of epididymal fat pads with leptin or its i.v. injection in conscious rats increased NO(3)-NO(2) release. The release of NO(3)-NO(2) in vivo and in vitro exceeded that of leptin by many fold, indicating that leptin activates NO synthase. Leptin increased tumor necrosis factor (TNF)-alpha release at a 100-fold lower dose than required for NO release in vitro and in vivo, suggesting that it also may participate in leptin-induced NO release. However, because many molecules of leptin were required to release a molecule of TNF-alpha in vivo and in vitro, we believe that leptin-induced TNF-alpha release is an associated phenomenon not involved in NO production. The results support the hypothesis that adipocytes play a major role in NO release by activating NO synthase in the adipocytes and the adjacent capillary endothelium.
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PMID:Resting and circadian release of nitric oxide is controlled by leptin in male rats. 1196 27

The present study compared the effect of dietary conjugated linolenic acid (CLNA) on body fat and serum and liver lipid levels with that of CLA in rats. FFA rich in linoleic acid, a-linolenic acid, CLA, or CLNA were used as experimental fats. Male Sprague-Dawley rats (4 wk old) were fed purified diets containing 1% of one of these experimental fats. After 4 wk of feeding, adipose tissue weights, serum and liver lipid concentrations, serum tumor necrosis factor (TNF)-alpha and leptin levels, and hepatic beta-oxidation activities were measured. Compared with linoleic acid, CLA and, more potently, CLNA were found to reduce perirenal adipose tissue weight. The same trend was observed in the weight of epididymal adipose tissue. CLNA, but not CLA, was found to significantly increase serum and liver TG concentrations. Serum FFA concentration was also increased in the CLNA group more than in the other groups. The activity of beta-oxidation in liver mitochondria and peroxisomes was significantly higher in the CLNA group than in the other groups. Thus, the amount of liver TG exceeded the ability of hepatic beta-oxidation. Significant positive correlation was found between the adipose tissue weights and serum leptin levels in all animals (vs. perirenal: r = 0.557, P < 0.001; vs. epididymal: r = 0.405, P < 0.05). A less significant correlation was found between adipose tissue weights and serum TNF-alpha level (vs. perirenal: r = 0.069, P > 0.1; vs. epididymal: r = 0.382, P < 0.05). Although the mechanism for the specific effect of CLNA is not clear at present, these findings indicate that in rats CLNA modulated the body fat and TG metabolism differently from CLA.
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PMID:Dietary conjugated linolenic acid in relation to CLA differently modifies body fat mass and serum and liver lipid levels in rats. 1203 Mar 14

In order to discover the effect of CLA on the body fat size and serum cytokine levels, four groups of male mice were fed diets containing either 1% linoleic acid (LA) or conjugated linoleic acid (CLA) with or without 0.2% sesamin for 8 weeks. The weight gain and feed efficiency were significantly lower in the CLA groups. CLA significantly reduced relative weights (g/100 g body weight) of epididymal and perirenal adipose tissues, in particular the former. Concentrations of serum TNF-alpha and leptin were significantly reduced by dietary CLA. Sesamin did not show additional effects in all of these parameters. There was a positive correlation between cytokine production and body-fat reducing potential of CLA. These results indicated that mice appeared to be a hyperresponder to dietary CLA insofar as the reduction of body fat size is concerned.
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PMID:Conjugated linoleic acid reduces body fats and cytokine levels of mice. 1203 77

The sympathetic nervous system plays a central role in lipolysis and the production of leptin in white adipose tissue (WAT). In this study, we have examined whether nerve growth factor (NGF), a target-derived neurotropin that is a key signal in the development and survival of sympathetic neurons, is expressed and secreted by white adipocytes. NGF mRNA was detected by RT-PCR in the major WAT depots of mice (epididymal, perirenal, omental, mesenteric, subcutaneous) and in human fat (subcutaneous, omental). In mouse WAT, NGF expression was observed in mature adipocytes and in stromal vascular cells. NGF expression was also evident in 3T3-L1 cells before and after differentiation into adipocytes. NGF protein, measured by ELISA, was secreted from 3T3-L1 cells, release being higher before differentiation. Addition of the sympathetic agonists norepinephrine, isoprenaline, or BRL-37344 (beta(3)-agonist) led to falls in NGF gene expression and secretion by 3T3-L1 adipocytes, as did IL-6 and the PPARgamma agonist rosiglitazone. A substantial decrease in NGF expression and secretion occurred with dexamethasone. In contrast, LPS increased NGF mRNA levels and NGF secretion. A major increase in NGF mRNA level (9-fold) and NGF secretion (<or=40-fold) in 3T3-L1 adipocytes occurred with TNF-alpha. RT-PCR showed that the genes encoding the p75 and trkA NGF receptors were expressed in mouse WAT. These results demonstrate that white adipocytes secrete NGF (an adipokine), NGF synthesis being influenced by several factors with TNF-alpha having a major stimulatory effect. We suggest that NGF is a target-derived neurotropin and an inflammatory response protein in white adipocytes.
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PMID:NGF gene expression and secretion in white adipose tissue: regulation in 3T3-L1 adipocytes by hormones and inflammatory cytokines. 1510 92

To find out whether the expressions of these adipocyte markers are influenced by oriental medicine, obesity rats induced by high fat diet (HFD) for 8 weeks were injected with 50 mg/100 g body weight adlay seed crude extract (ACE), daily for 4 weeks. The results are summarized as follows: HFD + ACE group significantly reduced food intakes and body weights. Weights of epididymal and peritoneal fat were dramatically increased in HFD groups compared with those of normal diet (ND) group but significantly decreased more in HFD + ACE group than those of HFD + saline group (sham). Those of brown adipocytes were increased in HFD + ACE group compared to ND and sham groups but there was no significant difference. The sizes in white adipose tissue (WAT) by microscope were markedly larger in HFD groups than ND group but considerably reduced in HFD + ACE group compared with sham group. The levels of triglyceride, total-cholesterol and leptin in blood serum were significantly decreased in HFD + ACE group compared to those of sham group. Leptin and TNF-alpha mRNA expressions in WAT of rats were remarkably increased more in sham group than in those of ND group. Those of HFD + ACE group were significantly decreased compared with those of sham group, especially. TNF-alpha mRNA expression in HFD + ACE group was declined more than that of ND group. In conclusion, treatments of ACE modulated expressions of leptin and TNF-alpha and reduced body weights, food intake, fat size, adipose tissue mass and serum hyperlipidemia in obesity rat fed HFD. Accordingly, the oriental medicine extract, adlay seed crude extract, can be considered for obesity therapies controlling.
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PMID:Hypolipidemic effects of crude extract of adlay seed (Coix lachrymajobi var. mayuen) in obesity rat fed high fat diet: relations of TNF-alpha and leptin mRNA expressions and serum lipid levels. 1523 96


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