Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cAMP-response element-binding protein-binding protein (CBP) and p300 are common coactivators for several transcriptional factors. It has been reported that both CBP and p300 are significant for the activation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is a crucial nuclear receptor in adipogenesis. However, it remains unclear whether CBP and/or p300 is physiologically essential to the activation of PPARgamma in adipocytes and adipocyte differentiation. In this study, we investigated the physiological significance of CBP/p300 in NIH3T3 cells transiently expressing PPARgamma and CBP and in 3T3-L1 preadipocytes stably expressing CBP- or p300-specific ribozymes. In PPARgamma-transfected NIH3T3 cells, induction of expression of PPARgamma target genes such as adipocyte fatty acid-binding protein (aP2) and lipoprotein lipase (LPL) by adding thiazolidinedione was enhanced, depending on the amount of a CBP expression plasmid transfected. Expression of aP2 and LPL genes, as well as glycerol-3-phosphate dehydrogenase activity and triacylglyceride accumulation after adipogenic induction, was largely suppressed in 3T3-L1 adipocytes expressing either the CBP- or p300-specific active ribozyme, but not in inactive ribozyme-expressing cells. These data suggest that both CBP and p300 are indispensable for the full activation of PPARgamma and adipocyte differentiation and that CBP and p300 do not mutually complement in the process.
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PMID:Overexpression and ribozyme-mediated targeting of transcriptional coactivators CREB-binding protein and p300 revealed their indispensable roles in adipocyte differentiation through the regulation of peroxisome proliferator-activated receptor gamma. 1188 4

The confluent cultures of 3T3-L1 fibroblasts were treated with or without bisphenol A (BPA) for 2 days and subsequently treated with insulin (INS) alone for 9 days. When BPA was absent during the first 2-day treatment period, the cultures contained 1.6 microg/microg DNA of triacylglycerol (TG), 202 mU/mg DNA of lipoprotein lipase (LPL) activity, and 462 nmol/min/mg DNA of glycerol-3-phosphate dehydrogenase (GPDH) activity. The presence of BPA during the same period caused a 150% increase in the TG content, a 60% increase in the LPL activity, and a 500% increase in the GPDH activity. Thus, BPA by itself can trigger 3T3-L1 fibroblasts to differentiate into adipocytes. Next, the confluent cultures were treated with BPA for 2 days and subsequently treated with a combination of INS and BPA for 9 days. The simultaneous presence of BPA with INS caused a 370% increase in the TG content, a 200% increase in the LPL activity, and a 225% increase in the GPDH activity compared with the cultures treated with INS alone. The amount of [(3)H]thymidine incorporated into DNA was lower in the cultures treated with INS in the presence of BPA than in those treated with INS alone, indicating that BPA has an anti-proliferative activity on 3T3-L1 cells. Taken together, our results indicate that BPA in combination with INS can accelerate the adipocyte conversion.
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PMID:Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. 1197 37

The putative role of nitric oxide (NO) in modulating adipogenesis was investigated in cultured preadipocytes derived from rat white adipose tissue. The NO releasing reagent, hydroxylamine (HA), and nitric oxide synthase (NOS) substrate L-arginine (Arg) had no influence on cell replication. However, both HA and Arg exhibited significant induction on differentiation, as evidenced by increased lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPDH) activities, as well as accelerated triacylglycerol (TG) accumulation. These observations suggested a positive role of NO in modulating adipogenesis. Preadipocytes were found to produce NO, and a approximately 50% increase over basal level was observed on the first 2 days of differentiation. Deprivation of endogenous NOS activity by a non-selective NOS inhibitor, N(G)-monomethyl-L-arginine (NMMA), partially abrogated the differentiation process, implicating a role for endogenous NO to stimulate preadipocyte differentiation. Both NOS isoforms, eNOS and iNOS, were detected in differentiating preadipocytes. Specific iNOS inhibitors (1400W and aminoguanidine) had little influence on NO production and differentiation, suggesting that eNOS rather than iNOS may be the major isoform involved in modulating adipogenesis.
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PMID:Nitric oxide promotes differentiation of rat white preadipocytes in culture. 1245 74

Fourteen Alpine goats at midlactation were fed a diet of hay and concentrate (55:45), without (control) or with formaldehyde-treated linseed (FLS) or oleic sunflower oil (OSO) at 11.2 or 3.5% of dry matter intake, respectively, in a 3 x 3 Latin Square design with three 3-wk periods. Milk yield was lower in goats fed FLS than control or OSO (2.13 vs. 2.32 kg/d). Milk fat content was higher with FLS or OSO than control (40.8 vs. 33.8 g/kg). Formaldehyde-treated linseed and OSO caused a significant decrease (23 and 18%, respectively) of C10 to C17 fatty acids secretion compared with control. The secretion of cis-9 C18:1 and cis-9, trans-11 C18:2 were increased 1.44- and 1.54-fold for FLS and 1.78- and 1.36-fold for OSO, compared with control. The C18:3 (n-3) secretion was increased 2.61-fold with FLS compared with control. Milk cis-9 C14:1/C14:0, cis-9 C16:1/C16:0, and cis-9 C18:1/C18:0 ratios decreased with the supplemented diets compared with control. Mammary stearoyl-CoA desaturase mRNA and activity were decreased by the lipid supplements, whereas no significant change was observed for acetyl-CoA carboxylase and fatty acid synthase. The activities of glucose-6-phosphate dehydrogenase, malic enzyme, and glycerol-3-phosphate dehydrogenase were not affected by the lipid supplements. Mammary lipoprotein lipase mRNA increased with OSO, whereas lipoprotein lipase activity tended to decrease with FLS compared with control. Milk lipoprotein lipase activity sharply decreased with lipid supplement (by 59 and 71%, for FLS and OSO, respectively). The changes in milk fatty acid profile due to FLS and OSO supplements were partly related to changes in the levels of mammary enzyme activities or mRNA.
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PMID:Mammary lipid metabolism and milk fatty acid secretion in alpine goats fed vegetable lipids. 1577 17

The adipocyte differentiation process involves a cascade of transcriptional events that culminates in the expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) and CCAAT/enhancer binding protein-alpha (C/EBPalpha). These adipogenic transcription factors regulate the expression of genes necessary for the development of mature adipocytes in mammals. The current study was undertaken to identify regulatory factors that affect adipogenesis and to analyze species-specific mRNA expression of factors involved in chicken adipocyte differentiation. We developed a system for differentiation of chicken (Gallus gallus) adipocytes in culture using medium containing 500 nM dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine, 20 microg/mL bovine insulin, 300 microM oleate, and 10% fetal bovine serum. The rapid differentiation of cells to mature adipocytes in this culture system was verified by observed increases in adipocyte fatty acid-binding protein (aP2) expression, glycerol-3-phosphate dehydrogenase (GPDH) activity and intracellular triglyceride accumulation. In contrast, cells cultured in a differentiation medium without fatty acids did not differentiate into mature adipocytes. The expression profiles of genes involved in the regulation of adipocyte differentiation, such as PPARgamma, C/EBPalpha, beta, delta, sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FAS), lipoprotein lipase (LPL), and glucose transporters 1 and 8 (GLUT1 and GLUT8) were studied. Rapid increases in PPARgamma and aP2 expression were observed after 9 and 12 h of culture in differentiation medium, respectively. In contrast, the expression patterns of the other adipogenic genes only differed slightly from those previously determined for mammalian adipocytes. These results suggest that exogenous fatty acid is essential for adipocyte differentiation in chickens, and that PPARgamma is possibly a key regulator in the early stages of chicken preadipocyte differentiation.
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PMID:Changes in mRNA expression of regulatory factors involved in adipocyte differentiation during fatty acid induced adipogenesis in chicken. 1592 39

Adipose tissue is an integral component within the endocrine system. Adipocytes produce numerous bioactive substances, and their dysregulation has serious pathophysiological consequences. We previously reported that human adipose tissue from several depots produces significant amounts of prolactin (PRL). To study locally produced PRL, we sought an acceptable in vitro model. Consequently, we developed an adipocyte cell line derived from a metastatic liposarcoma. The cell line, designated LS14, has been in continuous culture for 2 yr. These cells exhibit many properties of primary preadipocytes, including the ability to undergo terminal differentiation, as judged by morphological alterations, lipid accumulation, and increase in glycerol-3-phosphate dehydrogenase. LS14 cells express many adipose-associated genes, such as adipocyte fatty acid-binding protein (aP(2)), hormone-sensitive lipase, lipoprotein lipase, preadipocyte factor 1, adiponectin, leptin, and IL-6. Similar to primary adipocytes, LS14 cells also produce and respond to PRL, thus making them an attractive model to study adipose PRL production and function. The expression of PRL was confirmed at the transcriptional level by RT-PCR, and PRL secretion was determined by the Nb2 bioassay. Addition of exogenous PRL to LS14 cells resulted in a dose-dependent inhibition of IL-6 release. In summary, we have established a novel human adipocyte cell line with many characteristics of primary adipocytes. The LS14 cells open up new avenues for research on human adipocyte biology and add to the repertoire of nonpituitary, PRL-producing cell lines.
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PMID:LS14: a novel human adipocyte cell line that produces prolactin. 1619 5

Experimental butters with a high content of trans-18 : 1 fatty acids and/or cis-9,trans-11-18 : 2 (rumenic acid; RA) were fed to thirty-six New Zealand White rabbits to investigate their effects on adipose tissue (AT) and liver lipogenic activities. Animals received one of three atherogenic (0.2 % cholesterol) diets containing 12 % butter with either a standard fatty acid composition (rich in saturated fatty acids), rich in trans-10-18 : 1 (T10 diet) or in trans-11-18 : 1 plus RA (T11+ RA diet) for 6 or 12 weeks. The ingestion of butters rich in trans fatty acids and/or RA for 6 weeks had little or no effect on liver and AT lipogenesis. The ingestion for 12 weeks of butter rich in T11+ RA decreased perirenal AT weight, lipogenic enzyme and lipoprotein lipase activities, without affecting liver lipid concentration or lipogenic activities except for a decrease in glycerol-3-phosphate dehydrogenase activity. Similar trends, but of a lower magnitude, were observed in rabbits fed the T10 diet for 12 weeks. Ingestion of the T10 or T11+ RA diets for 6 or 12 weeks had no significant effect on plasma metabolites and hormones except for glucose which increased at 6 weeks in the T10 group. Plasma leptin concentration was positively correlated with AT weight but did not differ between the three diets. In conclusion, the supply of butters rich in either T10 or T11+ RA in an atherogenic diet for 12 weeks decreased rabbit AT lipogenesis, with a more marked effect of the T11+RA diet, but had no effect on liver lipogenesis.
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PMID:Effect of dietary supply of butters rich either in trans-10-18 : 1 or in trans-11-18 : 1 plus cis-9, trans-11-18 : 2 on rabbit adipose tissue and liver lipogenic activities. 1692 50

During fetal life, adipose tissue is predominantly comprised of brown or thermogenic adipocytes and there is a transition to white, lipid-storing adipocytes after birth concomitant with the onset of suckling. In pregnancies complicated by gestational diabetes, the fetus is hyperglycemic, has an increased fat mass, and is at increased risk of obesity in later life. In the present study, we have investigated the hypothesis that exposure to increased maternal nutrition during late gestation results in increased expression of genes that regulate adipogenesis and lipogenesis in perirenal fat in fetal sheep. Pregnant ewes were fed either at or approximately 55% above maintenance energy requirements during late pregnancy and quantitative RT-PCR was used to measure peroxisome proliferator-activated receptor gamma, lipoprotein lipase, glycerol-3-phosphate dehydrogenase, adiponectin, and leptin mRNA expression. We report that exposure to metabolic and hormonal signals of increased nutrition before birth results in an increase in the expression of the adipogenic factor, peroxisome proliferator-activated receptor gamma, and in lipoprotein lipase, adiponectin, and leptin mRNA expression in fetal perirenal fat. We propose that an increase in maternal, and hence fetal, nutrition results in a precocial increase in adipogenic, lipogenic, and adipokine gene expression in adipose tissue and that these changes may be important in the development of obesity in later life.
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PMID:Increased maternal nutrition stimulates peroxisome proliferator activated receptor-gamma, adiponectin, and leptin messenger ribonucleic acid expression in adipose tissue before birth. 1706 38

This work investigated the metabolic basis for the variability of carcass and i.m. adiposity in cattle. Our hypothesis was that the comparison of extreme breeds for adiposity might allow for the identification of some metabolic pathways determinant for carcass and i.m. adiposity. Thus, 23- to 28-mo-old steers of 3 breeds, 2 with high [Angus or Japanese Black x Angus (J. Black cross)] and 1 with low (Limousin) i.m. and carcass adiposity, were used to measure activities or mRNA levels, or both, of enzymes involved in de novo lipogenesis [acetyl-coA carboxylase, fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme], circulating triacylglycerol (TAG) uptake (lipoprotein lipase), and fatty acid esterification (glycerol-3-phosphate dehydrogenase), as well as the mRNA level of leptin, an adiposity-related factor. In a first study, enzyme activities were assayed in the s.c. adipose tissue (AT), the oxidative rectus abdominis, and the glycolytic semitendinosus muscles from steers finished for 6 mo. Compared with Angus or J. Black cross, Limousin steers had a 27% less (P = 0.003) rib fat thickness, and 23 and 29% less (P < or = 0.02) FAS and G6PDH activities in s.c. AT. In rectus abdominis and semitendinosus, the 75% less (P < 0.001) TAG content was concomitant with 50% less (P < 0.001) G6PDH activity. In a second study, enzyme activities plus mRNA levels were assayed in an oxido-glycolytic muscle, the longissimus thoracis (LT), in the i.m. AT dissected from LT, and in s.c. AT from the same Limousin steers and from Angus steers finished for 10 mo. Compared with Angus, the 50% less (P < 0.001) rib fat thickness in Limousin contrasted with the 1.1- to 5.8-fold greater (P < or = 0.02) mRNA levels or activities, or both, of acetyl-coA carboxylase, G6PDH, lipoprotein lipase, and glycerol-3-phosphate dehydrogenase in s.c. AT. Conversely, the 90% less (P < 0.001) TAG content in Limousin LT was concomitant to the 79 and 83% less (P < or = 0.002) G6PDH activity and leptin mRNA level. Such differences could arise from a greater number of adipocytes in LT from Angus steers because no difference was found between Limousin and Angus for G6PDH activity and leptin mRNA in i.m. AT. We conclude that FAS and G6PDH in s.c. AT could be involved in differences in carcass adiposity, but this relationship disappeared when the fatness increased strongly. Leptin and G6PDH are related to the expression of marbling whatever the body condition and thus could be relevant indicators of marbling in beef cattle.
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PMID:Glucose-6-phosphate dehydrogenase and leptin are related to marbling differences among Limousin and Angus or Japanese Black x Angus steers. 1759 7

Bitter melon (Momordica charantia; BM) has been shown to ameliorate diet-induced obesity and insulin resistance. To examine the effect of BM supplementation on cell size and lipid metabolism in adipose tissues, three groups of rats were respectively fed a high-fat diet supplemented without (HF group) or with 5 % lyophilised BM powder (HFB group), or with 0.01 % thiazolidinedione (TZD) (HFT group). A group of rats fed a low-fat diet was also included as a normal control. Hyperinsulinaemia and glucose intolerance were observed in the HF group but not in HFT and HFB groups. Although the number of large adipocytes (>180 microm) of both the HFB and HFT groups was significantly lower than that of the HF group, the adipose tissue mass, TAG content and glycerol-3-phosphate dehydrogenase activity of the HFB group were significantly lower than those of the HFT group, implying that BM might reduce lipogenesis in adipose tissue. Experiment 2 was then conducted to examine the expression of lipogenic genes in adipose tissues of rats fed low-fat, HF or HFB diets. The HFB group showed significantly lower mRNA levels of fatty acid synthase, acetyl-CoA carboxylase-1, lipoprotein lipase and adipocyte fatty acid-binding protein than the HF group (P < 0.05). These results indicate BM can reduce insulin resistance as effective as the anti-diabetic drug TZD. Furthermore, BM can suppress the visceral fat accumulation and inhibit adipocyte hypertrophy, which may be associated with markedly down regulated expressions of lipogenic genes in the adipose.
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PMID:Bitter melon (Momordica charantia L.) inhibits adipocyte hypertrophy and down regulates lipogenic gene expression in adipose tissue of diet-induced obese rats. 1765 27


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