Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.34 (lipoprotein lipase)
7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipose tissue distribution in man is dependent on genetic and environmental factors. The total and regional masses of adipose tissue are dependent on the number of adipocytes as well as their degree of filling with depot fat. Currently available evidence does not suggest a specific regional regulation of fat cell multiplication in subcutaneous depots, which instead seems to occur at a certain critical degree of filling of available adipocytes. The control of the rate of filling of adipocytes then seems to be the main factor determining the local, regional mass of adipose tissue. This in turn is regulated by the balance between the lipid accumulating and mobilization processes. The steroid hormones exert major permissive effects on these processes. It seems likely that the resulting effect of the rate of secretion of various steroid hormones, and the local density of their specific receptors, decide the regional distribution of body fat. Physiological and clinical situations with defined differences in these regulatory factors would then be expected to have characteristically different adipose tissue distribution. Sex differences include a larger subcutaneous adipose tissue in women than men, explainable at least partly by a depot in the gluteal-femoral region in women, which is essentially absent in non-obese men. Men on the other hand seem to have a larger proportion of their adipose tissue organ localized intra-abdominally. In addition, the gluteal-femoral fat cells are specifically enlarged in women, and have a higher lipoprotein lipase activity. While the larger adipose tissue in non-obese women may well be genetically linked, the specific characteristics of the gluteal-femoral adipocytes are most likely regulated by female sex steroid hormones. Another apparent sex difference is the ability of women to protect visceral depots from fat accumulation up to a certain degree of obesity, while men deposit excess fat in this region in parallel with other depots. This might, at least partly, simply be explainable by the smaller 'available space' in male than female adipose tissue. It should be emphasized that the effects of sex steroid hormones on the regulation of adipocyte metabolism occur only in concert with cortisol, which is always present. Cortisol itself expresses lipoprotein lipase activity as well as beta-adrenergic receptors (BARs), and probably has additional effects, not yet revealed. The net effect seems, however, to be lipid accumulation as seen in the apparently glucocorticoid receptor (GR) dense visceral adipose tissue in conditions of glucocorticoid excess, such as Cushing's syndrome. The effects of the sex steroid hormones should be regarded against this background.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adipose tissue distribution and function. 179 41

The effect of dexamethasone on lipoprotein lipase (LPL) gene expression during macrophage differentiation was investigated by using the human monocytic leukemia cell line THP-1 and human monocyte-derived macrophages. Addition of dexamethasone to THP-1 cells increased steady-state levels of LPL mRNA and LPL mass accumulation in the medium during PMA-induced differentiation by 4-fold. Studies with human monocyte-derived macrophages showed a similar effect of dexamethasone on LPL expression. Peak LPL mRNA levels were achieved 24-h post-dexamethasone addition to THP-1 cells. Optimal stimulation of LPL mRNA occurred when dexamethasone was added 24 h after induction with PMA. Thereafter, there was rapid decline in responsiveness to dexamethasone. Induction of LPL mRNA in THP-1 cells was completely blocked by actinomycin D, suggesting that induction was transcription dependent. The stability of LPL mRNA was not influenced by dexamethasone. Treatment of THP-1 cells with PMA led to a 2-fold increase in specific binding of dexamethasone and a 4-fold increase in glucocorticoid receptor mRNA within 12 h. Thus, dexamethasone stimulates LPL gene expression during differentiation of human macrophages, a process that involves induction of glucocorticoid receptor synthesis and activation.
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PMID:Transcriptional activation of the lipoprotein lipase gene in macrophages by dexamethasone. 200 46

Identification of three overlapping clones in a canine genomic lambda phage library allowed us to determine a detailed restriction enzyme map of the primary transcriptional unit of the pancreatic lipase gene (15.5 kilobase pairs) as well as 15 and 6 kilobase pairs of 5'- and 3'-flanking regions, respectively. DNA sequence analysis provided the primary structure of (a) 1,345 nucleotides (nt) of 5'-flanking sequence including CAAT and TATA boxes at positions -112 and -35, respectively, and a class 2 glucocorticoid receptor binding sequence at position -97, (b) 13,127 out of approximately 15,500 nt of the transcriptional unit which is organized into 13 exon sequences, and (c) 1,270 nt of 3'-flanking sequence. Exon 1 encodes the entire 5'-nontranslated mRNA sequence; exon 2, the ATG initiation codon and the hydrophobic portion of the signal peptide; and exon 6, Ser154 which shows homology to the active Ser152 in the porcine enzyme. Comparison of the amino acid sequences of human lipoprotein lipase, rat hepatic lipase, and Drosophila yolk proteins 1, 2, and 3 with canine pancreatic lipase shows that the central region of highest homology (encoded by exons 6-8 in the dog gene) contains four highly conserved subregions which may play a critical role in enzyme-substrate and protein-ligand binding for lipases and yolk proteins, respectively. Comparison of the sequences of 10 lipases from prokaryotes and eukaryotes identifies a 9-residue consensus sequence surrounding the active serine which includes the previously identified sequence Gly-X-Ser-X-Gly. The hydrophobic nature of this sequence in the 10 lipases contrasts with the hydrophilic nature of the corresponding sequences in serine proteases and thus defines an active site serine consensus sequence specific for lipases. An analysis of 5'- and 3'-flanking and intron 1-4 sequences in transient expression studies with AR4-2J and 266-6 cells was unable to reveal tissue-specific promoter or enhancer sequences.
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PMID:Structure of the canine pancreatic lipase gene. 250 43

Cortisol is known to induce lipoprotein lipase (LPL) activity in human adipose tissue in vitro and in vivo such as in Cushing's syndrome. The significance of the glucocorticoid receptor (GR) for this induction was evaluated in the present study. The synthetic steroid molecule RU 486, a potent glucocorticoid antagonist, was used as a tool to block the GR, in vitro and in vivo. In addition to LPL activity, glucose tolerance, blood pressure and plasma lipids, all variables influenced by cortisol, were studied in order to evaluate the peripheral antiglucocorticoid activity of RU 486 in vivo, in man. Addition of both cortisol and RU 486 to incubations of human adipose tissue pieces significantly inhibited the increase in LPL activity that could be induced by cortisol alone (p < 0.01). In a ten-fold molarity excess RU 486 totally abolished cortisol action (p < 0.01). With cortisol and RU 486 in equimolar concentrations the RU 486 blockade was probably incomplete and LPL activity induced (p < 0.05). The results imply that the stimulating effect of cortisol on LPL activity in human adipose tissue is mediated via the GR. Administration of 400 mg RU 486 at 2200 hours on two consecutive days to healthy men caused a significant rise in serum cortisol levels measured at 0800 hours (p < 0.05). The mean LPL activity in the subcutaneous abdominal adipose tissue remained unchanged. The mean level of serum triglycerides decreased significantly (p < 0.01) and there was a negative correlation between change in LPL activity and change in triglyceride levels (r = -0.73, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blockade of the glucocorticoid receptor with RU 486: effects in vitro and in vivo on human adipose tissue lipoprotein lipase activity. 762 71

Steroid hormones usually act via specific receptors and the hormone-receptor complex then influences the transcription of genes. These effects are often permissive for the actions of peptide hormones such as insulin and growth hormone (GH). The best known effects are those of cortisol. Since cortisol is always present, the sex steroids often modify cortisol effects. In adipose tissue, lipoprotein lipase (LPL), in the presence of insulin, is expressed via a glucocorticoid receptor, increasing transcription and stabilizing the enzyme. This process is efficiently inhibited by GH via posttranslational effects, and lipolysis is markedly stimulated. Testosterone inhibits LPL expression and, in the presence of GH, markedly increases lipolysis via multiple interactions along the lipolytic cascade. In human adipose tissue, direct effects of estrogen and progesterone cannot be demonstrated, probably because of the apparent absence of specific receptors. These hormones presumably via indirect mechanisms, perhaps by interaction with other hormone receptors.
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PMID:Growth hormone, insulin-like growth factor-I and lipid metabolism: interactions with sex steroids. 895 Jun 19

Hormones exert powerful influences on body fat distribution in humans. Studies under fully controlled conditions in vitro have indicated that cortisol and insulin facilitate lipid accumulation by expressing lipoprotein lipase (LPL). Growth hormone (GH) abolishes this and turns metabolism towards lipid mobilization. Testosterone and GH inhibit LPL and stimulate lipolysis markedly. Cortisol effects are mediated via a glucocorticoid receptor, and testosterone effects via an androgen receptor, the density of which appears to be higher in visceral than subcutaneous adipose tissue. The receptor-mediated effects are probably expressed via transcription of appropriate genes. The female sex steroids also regulate adipose tissue metabolism, but apparently not directly in the absence of specific cellular receptors. Oestrogens seem to exert net effects similar to those of testosterone. These results of cellular studies agree well with in-vivo studies of triglyceride uptake and turnover in different adipose tissue regions. Furthermore, clinical entities with characteristic disturbances in hormone levels show the expected redistribution patterns.
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PMID:Hormonal control of regional fat distribution. 940 18

The aim of the study was to investigate the possible interactions among the glucocorticoid receptor (GRL), lipoprotein lipase (LPL), and adrenergic receptor (ADR) genes on plasma insulin and lipid levels. The study was cross-sectional and based on 742 individuals from phase 2 of the Quebec Family Study (QFS) cohort. Gene markers were identified by Southern blot analysis or polymerase chain reaction (PCR). Plasma glucose and insulin in the fasted state and during an oral glucose tolerance test (OGTT) were determined and insulin and glucose areas were computed. Triglyceride (TG) and cholesterol concentrations in plasma and lipoprotein fractions were determined enzymatically. The results show that GRL and LPL variants had independent effects on plasma high-density lipoprotein cholesterol (HDL-C) and two beta2-ADR variants were related to total cholesterol concentrations. The alpha2-ADR gene Dral polymorphism was the only variant that had an independent effect on the plasma insulin area. Gene-gene interaction effects were found between GRL and alpha2-ADR genes for low-density lipoprotein cholesterol ([LDL-C] P = .013) and between GRL and LPL genes for HDL-C (P = .045). Higher-order interaction effects involving GRL, LPL, and ADR markers were observed for the plasma insulin area (P = .001 to .025) but not the glucose area. After correction for multiple tests, the findings remained essentially unchanged for the insulin area but became nonsignificant for the lipid phenotypes. In conclusion, multiple interactions among GRL, LPL, and ADR gene markers contribute to insulin metabolism and perhaps to lipid levels, while no significant effect is found for each gene separately. The LPL locus appears to determine the pattern of interactions with ADR and GRL loci. These results suggest that gene-gene interaction effects could play a role in the etiology of risk factors for common chronic diseases.
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PMID:Interactions among the glucocorticoid receptor, lipoprotein lipase, and adrenergic receptor genes and plasma insulin and lipid levels in the Quebec Family Study. 1122 37

In utero overexposure to glucocorticoids may explain the association between low birth weight and subsequent development of the metabolic syndrome. We previously showed that prenatal dexamethasone (dex) exposure in the rat lowers birth weight and programs adult fasting and postprandial hyperglycemia, associated with increased hepatic gluconeogenesis driven by elevated liver glucocorticoid receptor (GR) expression. This study aimed to determine whether prenatal dex (100 microg/kg per day from embryonic d 15 to embryonic d 21) programs adult GR expression in skeletal muscle and/or adipose tissue and whether this contributes to altered peripheral glucose uptake or metabolism. In utero dex-exposed rats remained lighter until 6 months of age, despite some early catch-up growth. Adults had smaller epididymal fat pads, with a relative increase in muscle size. Although glycogen storage was reduced in quadriceps, 2-deoxyglucose uptake into extensor digitorum longus muscle was increased by 32% (P < 0.05), whereas uptake in other muscles and adipose beds was unaffected by prenatal dex. GR mRNA was not different in most muscles but selectively reduced in soleus (by 23%, P < 0.05). However, GR mRNA was markedly increased specifically in retroperitoneal fat (by 50%, P < 0.02). This was accompanied by a shift from peroxisomal proliferator-activated receptor gamma 1 to gamma 2 expression and a reduction in lipoprotein lipase mRNA (by 28%, P < 0.02). Adipose leptin, uncoupling protein-3 and resistin mRNAs, muscle GLUT-4, and circulating lipids were not affected by prenatal dex. These data suggest that hyperglycemia in 6-month-old rats exposed to dexamethasone in utero is not due to attenuated peripheral glucose disposal. However, increased GR and attenuated fatty acid uptake specifically in visceral adipose are consistent with insulin resistance in this crucial metabolic depot and could indirectly contribute to increased hepatic glucose output.
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PMID:Programming of rat muscle and fat metabolism by in utero overexposure to glucocorticoids. 1258 77

Fatty acid metabolism is abnormal in insulin-resistant states that increase the risk of atherosclerosis such as type 2 diabetes and the metabolic syndrome. How fatty acids promote vascular disease is poorly understood, but lipoprotein lipase and peroxisome proliferator-activated receptor alpha (PPARalpha)-physiologically related proteins involved in fatty acid metabolism-may be involved. Glucocorticoid metabolism is also abnormal in insulin-resistant states and may promote several components of the metabolic syndrome. Recent studies have shown that hepatic fatty acid metabolism is required for the development of insulin resistance and hypertension caused by glucocorticoid excess, suggesting that crosstalk between glucocorticoid receptor-and PPARalpha-dependent pathways may contribute to vascular disease.
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PMID:Fatty acid metabolism and vascular disease. 1503 Jul 93

Perturbed prolactin (PRL) secretion and concomitant downregulation of PRL receptor (PRLR) in periparturient dams exposed to altered gravity are linked to aberrant lipogenesis and reduced neonatal survival. PRL and glucocorticoids (GC) are known to modulate PRLR expression. We hypothesized that improving levels of PRLR would mitigate the increased gravity [hypergravity (HG)]-induced effects of impaired mammary lipogenesis and increase neonatal survival. The objective of this study was to determine if prepartum PRL or GC supplementation would override the HG-induced repression of PRLR along with lipogenic genes and increase tissue fatty acid synthesis. Pregnant rats were exposed to either 2g (HG) or kept at 1g (control) from day 11 of gestation (G11) through Postnatal day 1 (P1). HG exposed rats were supplemented with either PRL or corticosterone or a placebo from G13 to P1. On P1, mammary, liver and adipose tissues were collected to measure glucose incorporation into lipids and mRNA abundance of PRL long and short form receptors (Prlr-l, Prlr-s), glucocorticoid receptor (Nr3c1), Acetyl CoA carboxylase-alpha (Acaca), fatty acid synthase (Fasn), lipoprotein lipase (Lpl), Sterol Regulatory Element Binding Protein-1 (Srebp1) and protein kinase B (Akt1) genes by quantitative polymerase chain reaction (qPCR). PRL and GC supplementation had a limited effect on lipogenesis in the three tissues of HG group likely due to their inability to increase abundance of key down-regulated genes, including Prlr-l and Nr3c1. There was no difference in the abundance of genes coding for milk proteins or those associated with milk fat globule formation and secretion. These data suggest that reduced lipogenesis in HG exposed dams is independent of PRL and GC secretion but may be associated with dysregulation of multiple metabolic regulators at the level of mRNA expression.
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PMID:Lipogenesis impaired in periparturient rats exposed to altered gravity is independent of prolactin and glucocorticoid secretion. 1866 86


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