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)

Acyl-CoAsynthetase (ACS) is a key gene for cellular utilization of long-chain fatty acids. We characterized its regulation by physiological concentrations of insulin that acutely regulate metabolism. Our results demonstrate that subnanomolar insulin rapidly and maximally stimulates ACS gene transcription in the absence of protein synthesis; 0.5 nM insulin produced a 2.3 +/- 0.1-fold increase in ACS mRNA levels and induced ACS gene transcription 2.4 +/- 0.3-fold. The insulin sensitivity of ACS was compared with lipoprotein lipase (LPL) and stearoyl-CoA desaturase-1 (SCD-1), which were both less sensitive to insulin. Physiological triiodothyronine (10 nm) also induced ACS mRNA 2.4 +/- 0.1-fold and gene transcription 2.8 +/- 0.3-fold and coordinately induced LPL and SCD-1 mRNA and gene transcription. Because insulin and adenosine 3',5'-cyclic monophosphate often regulate genes involved in lipid and carbohydrate metabolism in a reciprocal manner, we evaluated effects of 1-methyl-3-isobutylxanthine (MIX).ACS mRNA levels were strongly downregulated by MIX in a dose-dependent manner, and ACS gene transcription inhibited in a coordinate manner with LPL and SCD-1. These data demonstrate a uniquely sensitive pattern of stimulation of ACS gene transcription by insulin with reciprocal regulation by MIX, and they suggest a significant role for ACS as a tightly regulated "gatekeeper" gene participating in the control of adipocyte metabolism.
 ...
PMID:Physiological concentrations of insulin and T3 stimulate 3T3-L1 adipocyte acyl-CoA synthetase gene transcription. 896 77

The basis for the variation in fatty acid composition in different ovine adipose tissue depots was investigated. The proportion of stearic (C18:0) and oleic (C18:1) acids vary in a site-specific fashion; abdominal depots (omental and perirenal) contain relatively more C18:0 than C18:1, and carcass depots, especially sternum, have a markedly higher proportion of C18:1. Additionally, expression of a number of lipogenic enzyme genes (stearoyl-CoA desaturase [SCD], acetyl-CoA carboxylase-alpha [ACC-alpha], lipoprotein lipase [LPL]) and the cytoskeletal protein gene alpha-tubulin vary among depots, although the pattern of variation differs for each mRNA. When these expression data were related to the mean cell volume of adipocytes pooled from all depots, a significant pattern emerged: expression of the ACC-alpha, LPL, and alpha-tubulin genes was highly correlated with the size of adipocytes. In contrast, when the expression of SCD mRNA was assessed as a function of mean cell volume, two populations of adipocytes emerged: no significant correlation was found between the expression of SCD mRNA per adipocyte and mean cell volume for the abdominal depots, although a highly significant correlation was observed between SCD gene expression and mean cell volume for the carcass and epicardial depots. Similarly, a highly significant correlation was found for the amount of C18:1 per adipocyte and the abundance of SCD mRNA per adipocyte for the carcass and epicardial depots, whereas no significant correlation was observed for these traits for the omental and perirenal depots. Thus, the SCD gene seems to be regulated in a depot-specific fashion and in a manner distinct from that of the ACC and LPL genes.
 ...
PMID:Ovine adipose tissue monounsaturated fat content is correlated to depot-specific expression of the stearoyl-CoA desaturase gene. 1068 3

Our objective was to determine the influence of bovine growth hormone (bGH) and bovine growth hormone-releasing factor (bGRF) administration on the mRNA abundance of lipoprotein lipase (LpL) and stearoyl-CoA desaturase (SCD). Primiparous Holstein cows received bGH, bGRF, or no treatment from 118 to 181+/-1 d postpartum. We hypothesized that bGH and bGRF treatment would increase the mRNA abundance of both SCD and LpL in the mammary gland with a corresponding reduction in adipose tissue. Milk yield significantly increased but milk fat percentage did not change as a result of bGH or bGRF treatment. Short-, medium-, and long-chain fatty acid concentrations in milk were not affected by either bGH or bGRF treatments, with the exception of a modest, but significant, increase in C16:1 and C18:1 following bGH treatment. Analysis was conducted on the genes encoding LpL (E.C. 3.3.1.34), a key enzyme involved in the uptake of fatty acids into tissues, and SCD (E.C. 1.14.99.5), which is the enzyme responsible for introducing delta9 double bonds in fatty acids of 16 and 18 carbons in length. In adipose tissue, treatment with bGH and bGRF reduced the mRNA abundance of LpL to 14.6 and 25.7% respectively, of that observed for control animals. Similarly, these treatments reduced the SCD mRNA abundance to undetectable levels in adipose tissue. In mammary gland, bGH and bGRF had no significant impact on LpL mRNA abundance. Bovine GH did not significantly affect SCD mRNA abundance in the mammary gland, and bGRF reduced SCD mRNA abundance. From this study to examine the role of bGH and bGRF on the expression of the genes encoding these key lipogenic enzymes in cattle, we conclude that the increased substrate required for enhanced milk fatty acid yield may have been provided through redirection of nutrients to the mammary gland away from adipose tissue and through overall increased metabolism in the mammary gland.
 ...
PMID:Influence of bovine growth hormone and growth hormone-releasing factor on messenger RNA abundance of lipoprotein lipase and stearoyl-CoA desaturase in the bovine mammary gland and adipose tissue. 1070 33

Numerous physiological effects are attributed to conjugated linoleic acid (CLA). The purpose of this presentation is to consider these effects with respect to the cis-9,trans-11 and trans-10,cis-12 CLA isomers. We review previously published data and present new findings that relate to underlying biochemical mechanisms of action. Both isomers are natural products. The cis-9,trans-11 isomer is the principal dietary form of CLA, but the concentrations of this isomer and the trans-10,cis-12 isomer in dairy products or beef vary depending on the diet fed to cows or steers, respectively. The trans-10,cis-12 CLA isomer exerts specific effects on adipocytes, in particular reducing the uptake of lipid by inhibiting the activities of lipoprotein lipase and stearoyl-CoA desaturase. The trans-10,cis-12 CLA isomer also affects lipid metabolism in cultured Hep-G2 human liver cells, whereas both the cis-9,trans-11 and trans-10,cis-12 CLA isomers appear to be active in inhibiting carcinogenesis in animal models. We present new findings indicating that the cis-9,trans-11 CLA isomer enhances growth and probably feed efficiency in young rodents. Accordingly, the effects of CLA on body composition (induced by trans-10,cis-12 CLA) and growth/feed efficiency (induced by cis-9,trans-11 CLA) appear to be due to separate biochemical mechanisms. We also show that a 19-carbon CLA cognate (conjugated nonadecadienoic acid, CNA) inhibits lipoprotein lipase activity as effectively as CLA in cultured 3T3-L1 adipocytes. Presumably, CNA is metabolized differently than the 18-carbon CLA isomers, so this finding indicates direct activity of the administered compound as opposed to acting via a metabolite.
 ...
PMID:The biologically active isomers of conjugated linoleic acid. 1141 93

Sixteen Holstein cows in mid-lactation were used to determine whether alterations of mammary fatty acid metabolism are responsible for the milk fat depression associated with consumption of fish oil. Cows were given a total mixed ration with no added fish oil (control), unprotected fish oil (3.7 % of dry matter), or glutaraldehyde-protected microcapsules of fish oil (1.5% or 3.0% of dry matter) for 4 weeks. Milk samples were taken once a week and a mammary biopsy was taken from a rear quarter at the end of the treatment period. Milk fat content was lower in cows given unprotected fish oil (26.0 g/kg), 1.5% protected fish oil (24.6 g/kg) and 3% protected fish oil (20.4 g/kg) than in cows fed the control diet (36.0 g/kg). This was mainly due to a decrease in the synthesis of short-chain fatty acids. Consumption of protected fish oil decreased the abundance of lipogenic enzymes mRNA in the mammary gland. Acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase mRNAs for cows given 3% protected fish oil averaged only 30%, 25% and 25% of control values, respectively. Dietary addition of unprotected fish oil slightly decreased mRNA abundance of these enzymes but markedly reduced the amount of lipoprotein lipase mRNA. Milk fat content was significantly correlated with gene expression of acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase but not lipoprotein lipase. These results suggest that fish oil reduces milk fat percentage by inhibiting gene expression of mammary lipogenic enzymes.
 ...
PMID:Addition of fish oil to diets for dairy cows. II. Effects on milk fat and gene expression of mammary lipogenic enzymes. 1246 90

Lecithin-cholesterol acyltransferase deficiency is frequently associated with hypertriglyceridemia (HTG) in animal models and humans. We investigated the mechanism of HTG in the ldlr-/- x lcat-/- (double knockout (dko)) mice using the ldlr-/- x lcat+/+ (knock-out (ko)) littermates as control. Mean fasting triglyceride (TG) levels in the dko mice were elevated 1.75-fold compared with their controls (p < 0.002). Both the very low density lipoprotein and the low density lipoprotein/intermediate density lipoprotein fractions separated by fast protein liquid chromatography were TG-enriched in the dko mice. In vitro lipolysis assay revealed that the dko mouse very low density lipoprotein (d < 1.019 g/ml) fraction separated by ultracentrifugation was a more efficient substrate for lipolysis by exogenous bovine lipoprotein lipase. Post-heparin lipoprotein lipase activity was reduced by 61% in the dko mice. Hepatic TG production rate, determined after intravenous Triton WR1339 injection, was increased 8-fold in the dko mice. Hepatic mRNA levels of sterol regulatory element binding protein-1 (srebp-1) and its target genes acetyl-CoA carboxylase-1 (acc-1), fatty acid synthase (fas), and stearoyl-CoA desaturase-1 (scd-1) were significantly elevated in the dko mice compared with the ko control. The hepatic mRNA levels of LXRalpha (lxralpha) and its target genes including angiopoietin-like protein 3 (angptl-3) in the dko mice were unchanged. Fasting glucose and insulin levels were reduced by 31 and 42%, respectively in the dko mice, in conjunction with a 49% reduction in hepatic pepck-1 mRNA (p = 0.014). Both the HTG and the improved fasting glucose phenotype seen in the dko mice are at least in part attributable to an up-regulation of the hepatic srebp-1c gene.
 ...
PMID:Hypertriglyceridemia in lecithin-cholesterol acyltransferase-deficient mice is associated with hepatic overproduction of triglycerides, increased lipogenesis, and improved glucose tolerance. 1466 45

Milk fat has a large effect on nutritional, technological and sensorial properties of milk products. The milk fat content and composition are modulated by genetics and nutritional factors and imply a large number of enzymes. The regulation of their gene expression in the mammary gland still needs to be clarified. An association between the extensive polymorphism at the alphas1-casein (alphas1-Cas) locus and both the lipid content and the characteristics of this fraction in caprine milk has been demonstrated. In order to decipher the mechanism responsible for this impact, a quantification of the transcripts of four lipogenic key enzymes (acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase and stearoyl-CoA desaturase) was performed using real-time RT-PCR, suggesting an absence of association between the alphas1-Cas genotype and expression variability of the studied genes. This approach has been completed by a more global analysis using a first generation of ruminant macroarray gathering 400 gene probes. The comparison of the expression profiles of lactating goat alphas1-Cas A/A (strong allele) and F/F (defective allele) mammary gland allowed to confirm the expected variability in the expression of known genes (such as those encoding the alphas1-casein) in ruminant mammary tissues as well as to identify up- and down-regulated genes. A second generation of ruminant cDNA macroarray extended to a few thousands of genes is currently in progress and will be applied to study different factors such as the nutritional regulation of gene expression in the mammary gland.
 ...
PMID:Real-time RT-PCR and cDNA macroarray to study the impact of the genetic polymorphism at the alphas1-casein locus on the expression of genes in the goat mammary gland during lactation. 1500 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.
 ...
PMID:Mammary lipid metabolism and milk fatty acid secretion in alpine goats fed vegetable lipids. 1577 17

Many homeostatic processes, including appetite and food intake, are controlled by neuroendocrine circuits involving the CNS. The CNS also directly regulates adipocyte metabolism, as we have shown here by examining central action of the orexigenic hormone ghrelin. Chronic central ghrelin infusion resulted in increases in the glucose utilization rate of white and brown adipose tissue without affecting skeletal muscle. In white adipocytes, mRNA expression of various fat storage-promoting enzymes such as lipoprotein lipase, acetyl-CoA carboxylase alpha, fatty acid synthase, and stearoyl-CoA desaturase-1 was markedly increased, while that of the rate-limiting step in fat oxidation, carnitine palmitoyl transferase-1alpha, was decreased. In brown adipocytes, central ghrelin infusion resulted in lowered expression of the thermogenesis-related mitochondrial uncoupling proteins 1 and 3. These ghrelin effects were dose dependent, occurred independently from ghrelin-induced hyperphagia, and seemed to be mediated by the sympathetic nervous system. Additionally, the expression of some fat storage enzymes was decreased in ghrelin-deficient mice, which led us to conclude that central ghrelin is of physiological relevance in the control of cell metabolism in adipose tissue. These results unravel the existence of what we believe to be a new CNS-based neuroendocrine circuit regulating metabolic homeostasis of adipose tissue.
 ...
PMID:Ghrelin action in the brain controls adipocyte metabolism. 1676 21

Our objectives were 2-fold: to determine the effect of dietary linoleate on milk fat composition and on transcript abundance of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), lipoprotein lipase (LPL), and stearoyl-CoA desaturase (SCD) mRNA in mammary tissue, and to evaluate milk somatic cell mRNA as a source of mammary tissue mRNA for these enzymes. Eighteen primiparous, crossbred beef cows (BW = 411 +/- 24 kg; BCS = 5.25) were offered Foxtail millet hay at 1.68% of BW daily and either a low-fat control (n = 9) or a high-linoleate (79% 18:2n-6), cracked safflower seed supplement (n = 9). Diets were isonitrogenous and isocaloric, and the linoleate diet contained 5.4% of DMI as fat. At slaughter (37 +/- 3 d postpartum), mammary tissue was sampled and immediately frozen in liquid N2 before being stored at -80 degrees C. Milk samples were obtained from the same mammary glands and immediately centrifuged at 1,200 x g to pellet somatic cells. A ribonuclease protection assay was used to quantify the mRNA in the mammary gland and milk somatic cells. Effects of diet, tissue, or their interaction were not observed for ACC (P = 0.28, 0.89, and 0.35, respectively), FAS (P = 0.38, 0.66, and 0.20, respectively), LPL (P = 0.09, 0.15, and 0.43, respectively), or SCD (P = 0.45, 0.19, and 0.29, respectively). Dietary effects on fatty acid profile of the milk fat suggested that linoleate supplementation might have decreased de novo lipogenesis while increasing uptake of dietary fatty acids; this effect was consistent with a trend toward greater LPL mRNA for linoleate-fed cows (P = 0.09). Correlations (r values) between mammary tissue and milk somatic cell data for each mRNA for the low-fat control diet were: ACC, 0.76 (P = 0.02); FAS, 0.69 (P = 0.04); LPL, 0.68 (P = 0.04); and SCD, 0.73 (P = 0.05), and for the linoleate diet were: ACC, 0.85 (P = 0.003); FAS, 0.75 (P = 0.02); LPL, 0.90 (P = 0.001); and SCD, 0.73 (P = 0.03). We conclude that milk somatic cells obtained from lactating beef cows can be used as a source of RNA to study nutritional regulation of mammary gland lipogenesis in cows fed dietary fat supplements.
 ...
PMID:Evaluation of milk somatic cells as a source of mRNA for study of lipogenesis in the mammary gland of lactating beef cows supplemented with dietary high-linoleate safflower seeds. 1690 43


1 2 3 4 5 6 Next >>