Stimulation of lipoprotein lipase synthesis by refeeding, insulin and dexamethasone.
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ABSTRACT:
SUBMITTER: Oliver JD
PROVIDER: S-EPMC1134241 | biostudies-other | 1993 Jun
REPOSITORIES: biostudies-other
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Project description:Lipoprotein lipase (LPL) activity in cultured ventricular cardiomyocytes from adult rat hearts was stimulated by the combination of insulin (100 nM) and dexamethasone (100 nM) during an overnight (16 h) incubation. Wortmannin (100 nM), rapamycin (30 ng/ml) or PD98059 (50 microM) did not prevent this stimulation, suggesting that phosphatidylinositol 3-kinase, p70 S6 kinase and the mitogen-activated protein kinase cascade are not involved in transducing the hormonal signal. In contrast, cytochalasin D (2 microM) completely abolished the stimulatory effect of insulin and dexamethasone on both heparin-releasable LPL and total cellular LPL activities. The potential role of the actin cytoskeleton in the stimulation of LPL activity by insulin and dexamethasone appears to be distal to the initial signalling events since cytochalasin D is still effective in preventing the stimulation when added 2 h after the hormones.
| S-EPMC1220275 | biostudies-other
Project description:Lipoprotein lipase (LPL) activity was studied in rat cardiomyocytes after overnight culture (16 h) in the presence of insulin (100 nM) and/or dexamethasone (100 nM). Insulin in combination with dexamethasone (INS/DEX) increased heparin-releasable LPL activity by 71% over the control level (566+/-85 versus 331+/-48 nmol/h.mg cell protein). This was accompanied by a 61% increase in total cellular LPL activity (914+/-89 versus 567+/-64 nmol/h.mg cell protein). The increase in LPL activity occurred at sub-nanomolar concentrations of the hormones, but neither hormone was effective alone. LPL protein mass, quantified by ELISA, was the same in both control and INS/DEX-treated cells (27.7 versus 28.6 ng/mg cell protein, respectively), thus LPL specific activity in cardiomyocytes was increased by INS/DEX treatment (0.113 versus 0.069 mU/ng LPL protein). These findings emphasize the importance of hormonal interactions in the regulation of LPL in heart tissue.
| S-EPMC1218813 | biostudies-other
Project description:Lipoprotein lipase (LPL) is responsible for the intravascular catabolism of triglyceride-rich lipoproteins and plays a central role in whole-body energy balance and lipid homeostasis. As such, LPL is subject to tissue-specific regulation in different physiological conditions, but the mechanisms of this regulation remain incompletely characterized. Previous work revealed that LPL comprises a set of proteoforms with different isoelectric points, but their regulation and functional significance have not been studied thus far. Here we studied the distribution of LPL proteoforms in different rat tissues and their regulation under physiological conditions. First, analysis by two-dimensional electrophoresis and Western blot showed different patterns of LPL proteoforms (i.e., different pI or relative abundance of LPL proteoforms) in different rat tissues under basal conditions, which could be related to the tissue-specific regulation of the enzyme. Next, the comparison of LPL proteoforms from heart and brown adipose tissue between adults and 15-day-old rat pups, two conditions with minimal regulation of LPL in these tissues, yielded virtually the same tissue-specific patterns of LPL proteoforms. In contrast, the pronounced down-regulation of LPL activity observed in white adipose tissue during fasting is accompanied by a prominent reconfiguration of the LPL proteoform pattern. Furthermore, refeeding reverts this down-regulation of LPL activity and restores the pattern of LPL proteoforms in this tissue. Importantly, this reversible proteoform-specific regulation during fasting and refeeding indicates that LPL proteoforms are functionally diverse. Further investigation of potential differences in the functional properties of LPL proteoforms showed that all proteoforms exhibit lipolytic activity and have similar heparin-binding affinity, although other functional aspects remain to be investigated. Overall, this study demonstrates the ubiquity, differential distribution and specific regulation of LPL proteoforms in rat tissues and underscores the need to consider the existence of LPL proteoforms for a complete understanding of LPL regulation under physiological conditions.
2024-01-26 | PXD043704 | Pride
Project description:Background and aimsOur aim was to gain insight into the role that lipoprotein lipase (LPL) and hepatic lipase (HL) plays in HDL metabolism and to better understand LPL- and HL-deficiency states.MethodsWe examined the apolipoprotein (apo) A-I-, A-II-, A-IV-, C-I-, C-III-, and E-containing HDL subpopulation profiles, assessed by native 2-dimensional gel-electrophoresis and immunoblotting, in 6 homozygous and 11 heterozygous LPL-deficient, 6 homozygous and 4 heterozygous HL-deficient, and 50 control subjects.ResultsLPL-deficient homozygotes had marked hypertriglyceridemia and significant decreases in LDL-C, HDL-C, and apoA-I. Their apoA-I-containing HDL subpopulation profile was shifted toward small HDL particles compared to controls. HL-deficient homozygotes had moderate hypertriglyceridemia, modest increases in LDL-C and HDL-C level, but normal apoA-I concentration. HL-deficient homozygotes had a unique distribution of apoA-I-containing HDL particles. The normally apoA-I:A-II, intermediate-size (α-2 and α-3) particles were significantly decreased, while the normally apoA-I only (very large α-1, small α-4, and very small preβ-1) particles were significantly elevated. In contrast to control subjects, the very large α-1 particles of HL-deficient homozygotes were enriched in apoA-II. Homozygous LPL- and HL-deficient subjects also had abnormal distributions of apo C-I, C-III, and E in HDL particles. Values for all measured parameters in LPL- and HL-deficient heterozygotes were closer to values measured in controls than in homozygotes.ConclusionsOur data are consistent with the concept that LPL is important for the maturation of small discoidal HDL particles into large spherical HDL particles, while HL is important for HDL remodeling of very large HDL particles into intermediate-size HDL particles.
| S-EPMC5064856 | biostudies-literature
Project description:OBJECTIVE:To determine whether n-3 fatty acids (n-3) influence arterial cholesterol delivery and lipoprotein lipase (LpL) levels in insulin-resistant mice. METHODS AND RESULTS:Insulin resistance contributes to risk of cardiovascular disease. It was previously reported that saturated fat (SAT) diets increased, but n-3 diets decreased, arterial low-density lipoprotein (LDL) cholesterol deposition from LDL total and selective uptake; this was associated with increased or decreased arterial LpL, respectively. Insulin receptor transgenic knockout mice (L1) were fed a chow, SAT, or n-3 diet for 12 weeks. Double-fluorescent boron dipyrromethene (BODIPY)-cholesteryl ester (CE) and Alexa dye-labeled human LDL were injected to separately trace LDL-CE and LDL-apolipoprotein B whole particle uptake. In contrast to SAT, n-3 diets markedly reduced all plasma lipids, ameliorating progression of insulin resistance. As opposed to SAT, n-3 reduced arterial LDL uptake, CE deposition, and selective uptake. Disparate patterns of CE deposition between diets were comparable with arterial LpL distribution; SAT induced high LpL levels throughout aortic media; LpL was limited only to intima in n-3-fed mice. CONCLUSIONS:n-3 diets diminish arterial LDL-cholesterol deposition in mice with insulin resistance, and this is associated with changes in arterial LpL levels and distribution.
| S-EPMC3107680 | biostudies-literature
Project description:In previous studies, we demonstrated that down-regulation of lipoprotein lipase in L6 muscle cells increased insulin-stimulated glucose uptake. In the current study, we used RNA interference technology to silence the LPL gene in L6 cells and generate a LPL-knock-down (LPL-KD) cell line. ShRNA transfected cells showed a 88% reduction in the level of LPL expression. The metabolic response to insulin was compared in wild-type (WT) and LPL-KD cells. Insulin-stimulated glycogen synthesis and glucose oxidation were respectively, 2.4-fold and 2.6-fold greater in LPL-KD cells compared to WT cells. Oxidation of oleic acid was reduced by 50% in LPL-KD cells compared to WT cells even in the absence of insulin. The contribution of LPL in regulating fuel metabolism was confirmed by adding back purified LPL to the culture media of LPL-KD cells. The presence of 10 μg/mL LPL resulted in LPL-KD cells reverting back to lower glycogen synthesis and glucose oxidation and increased fatty acid oxidation. Thus, LPL depletion appeared to mimic the action of insulin. These finding suggests an inverse correlation between muscle LPL levels and insulin-stimulated fuel homeostasis.
| S-EPMC4442086 | biostudies-literature
Project description:Lysosomal acid lipase (LAL) hydrolyses cholesteryl esters and triacylglycerols (TG) within lysosomes to mobilise NEFA and cholesterol. Since LAL-deficient (Lal (-/-) ) mice suffer from progressive loss of adipose tissue and severe accumulation of lipids in hepatic lysosomes, we hypothesised that LAL deficiency triggers alternative energy pathway(s).We studied metabolic adaptations in Lal (-/-) mice.Despite loss of adipose tissue, Lal (-/-) mice show enhanced glucose clearance during insulin and glucose tolerance tests and have increased uptake of [(3)H]2-deoxy-D-glucose into skeletal muscle compared with wild-type mice. In agreement, fasted Lal (-/-) mice exhibit reduced glucose and glycogen levels in skeletal muscle. We observed 84% decreased plasma leptin levels and significantly reduced hepatic ATP, glucose, glycogen and glutamine concentrations in fed Lal (-/-) mice. Markedly reduced hepatic acyl-CoA concentrations decrease the expression of peroxisome proliferator-activated receptor ? (PPAR?) target genes. However, treatment of Lal (-/-) mice with the PPAR? agonist fenofibrate further decreased plasma TG (and hepatic glucose and glycogen) concentrations in Lal (-/-) mice. Depletion of hepatic nuclear factor 4? and forkhead box protein a2 in fasted Lal (-/-) mice might be responsible for reduced expression of microsomal TG transfer protein, defective VLDL synthesis and drastically reduced plasma TG levels.Our findings indicate that neither activation nor inactivation of PPAR? per se but rather the availability of hepatic acyl-CoA concentrations regulates VLDL synthesis and subsequent metabolic adaptations in Lal (-/-) mice. We conclude that decreased plasma VLDL production enhances glucose uptake into skeletal muscle to compensate for the lack of energy supply.
| S-EPMC4930475 | biostudies-literature
Project description:Lipoprotein lipase (Lpl) was predicted as a causal gene for abdominal using a novel statistical method named LCMS (Schadt et al., 2005, Nature Genetics). In order to validate this prediction, we profiled the liver tissues of lipoprotein lipase heterozygous knockout mice (Lpl+/-) and their littermate wild-type (wt) controls to examine the gene expression signature as well as pathways/networks resulting from the single gene perturbation.
2009-03-08 | GSE11991 | GEO
Project description:Lipoprotein lipase (Lpl) was predicted as a causal gene for abdominal using a novel statistical method named LCMS (Schadt et al., 2005, Nature Genetics). In order to validate this prediction, we profiled the liver tissues of lipoprotein lipase heterozygous knockout mice (Lpl+/-) and their littermate wild-type (wt) controls to examine the gene expression signature as well as pathways/networks resulting from the single gene perturbation. 8 Lpl+/- mice and 8 wt controls were profiled. Reference pool included RNA extracted from the liver of 9 wt control mice. Dye-swap was involved in the profiling.
2009-03-07 | E-GEOD-11991 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (Ahr), a ligand-activated transcriptional factor, mediates the transcriptional activation of a battery of genes encoding drug metabolism enzymes. In the present study, we investigated the hepatic mRNA expression profile in Ahr-null (Ahr KO) mice compared to wild-type mice by microarray analysis to find new Ahr target genes. Pooled total RNA samples of liver extracted from 7- and 60-week-old Ahr KO or wild-type mice were studied by DNA microarray representing 19,867 genes. It was demonstrated that 23 genes were up-regulated and 20 genes were down-regulated over 2 fold in Ahr KO mice compared with wild-type mice commonly within the different age groups. We focused on insulin-like growth factor binding protein-1 (Igfbp-1) and lipoprotein lipase (Lpl) that were up-regulated in Ahr KO mice. The higher expression in Ahr KO mice compared to wild-type mice were confirmed by real-time RT-PCR analysis. In the wild-type mice but not in the Ahr KO mice, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment increased the Igfbp-1 and Lpl mRNA levels. The expression profile of Igfbp-1 protein was consistent with that of Igfbp-1 mRNA. Since Lpl is the primary enzyme responsible for hydrolysis of lipids in lipoproteins, the serum triglyceride levels were determined. Indeed, the serum triglyceride levels in Ahr KO mice was lower than that in wild-type mice in accordance with the Lpl mRNA levels. Contrary to our expectation, TCDD treatment significantly increased the serum triglyceride levels in wild-type, but did not in Ahr KO mice. These results suggest that serum triglyceride levels are not correlated with hepatic Lpl expression levels. In the present study, we found that Ahr paradoxically regulates Igfbp-1 and Lpl expressions in the liver.
| S-EPMC7217312 | biostudies-literature