scholarly journals Post-transcriptional mechanisms are responsible for the reduction in lipoprotein lipase activity in cardiomyocytes from diabetic rat hearts

1995 ◽  
Vol 310 (1) ◽  
pp. 67-72 ◽  
Author(s):  
R Carroll ◽  
L Liu ◽  
D L Severson
Keyword(s):  
Lipoprotein Lipase ◽  
Total Protein ◽  
Specific Activity ◽  
Inhibitory Effect ◽  
Diabetic Rat ◽  
Mrna Levels ◽  
Rat Hearts ◽  
Mrna Content ◽  
Enzyme Specific Activity ◽  
Lpl Mass

Lipoprotein lipase (LPL) activity is reduced in cardiomyocytes from rat hearts following the acute (4-5 day) induction of diabetes with 100 mg/kg streptozotocin. The molecular basis for this inhibitory effect of diabetes on LPL activity was investigated by measuring steady-state LPL mRNA content and the synthesis and turnover of LPL protein ([35S]methionine incorporation into immunoprecipitable LPL protein in pulse and pulse-chase experiments) in control and diabetic cardiomyocytes. LPL activity was reduced to approx. 50% of control in diabetic cardiomyocytes, but LPL mRNA levels and turnover (degradation) of newly synthesized LPL were unchanged. Synthesis of total protein and LPL were reduced to 72% and 71% of control respectively; therefore, relative rates of LPL synthesis were the same in control and diabetic cardiomyocytes. The diabetes-induced reduction in LPL synthesis was accompanied by a decrease in LPL mass to 78% of control, and a decrease in enzyme specific activity (0.48 to 0.33 m-unit/ng of LPL protein) since the decline in catalytic activity was greater than the decrease in LPL synthesis and mass. Thus, post-transcriptional mechanisms involving a reduction in LPL synthesis as part of a generalized decrease in total protein synthesis, together with a post-translational mechanism(s) that result in accumulation of inactive LPL protein, are responsible for the decreased LPL activity in cardiomyocytes from diabetic rat hearts.

Diurnal rhythms and effects of fasting and refeeding on rat adipose tissue lipoprotein lipase

1996 ◽  
Vol 271 (6) ◽  
pp. E1092-E1097 ◽  
Author(s):  
M. Bergo ◽  
G. Olivecrona ◽  
T. Olivecrona
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Specific Activity ◽  
Early Morning ◽  
Diurnal Rhythms ◽  
Mrna Levels ◽  
Short Term ◽  
Early Afternoon ◽  
Rat Adipose Tissue ◽  
Adipose Tissue Lipoprotein Lipase

The activity of lipoprotein lipase (LPL) in adipose tissue is modulated by changes in the nutritional status. We have measured LPL activity, mass, and mRNA levels in rat adipose tissue during normal feeding cycles, during short- and long-term fasting, and during refeeding after fasting. LPL activity displayed a diurnal rhythm. The activity was highest during the night and early morning, decreased to a minimum during the early afternoon, and then increased again. These changes corresponded to the feeding pattern. The increases and/or decreases resulted from changes in LPL synthetic rate compounded by posttranslational mechanisms. During short-term fasting, LPL specific activity decreased to < 30% of control. The specific activity was restored within 4 h by refeeding. On longer fasting, LPL mRNA decreased. This became significant from 36 h. On refeeding, it took 12 h to restore the mRNA levels, whereas tissue LPL activity and mass could not be fully restored by 36 h of refeeding. These data show that LPL activity during short-term fasting is regulated posttranscriptionally, which allows for quick upregulation after refeeding. On longer fasting, other mechanisms affecting LPL transcription and synthesis come into play, and upregulation after refeeding is slowed down.

Regulation of lipoprotein lipase activity in cardiac myocytes from control and diabetic rat hearts by plasma lipids

1992 ◽  
Vol 70 (9) ◽  
pp. 1271-1279 ◽  
Author(s):  
Brian Rodrigues ◽  
Janice E. A. Braun ◽  
Michael Spooner ◽  
David L. Severson
Keyword(s):  
Lipoprotein Lipase ◽  
Cardiac Myocytes ◽  
Lipase Activity ◽  
Plasma Lipids ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Lipoprotein Lipase Activity ◽  
Triton Wr 1339 ◽  
Plasma Triacylglycerol

The objective of this investigation was to test the hypothesis that the diabetes-induced reduction in lipoprotein lipase activity in cardiac myocytes may be due to hypertriglyceridemia. Administration of 4-aminopyrazolopyrimidine (50 mg/kg) to control rats for 24 h reduced plasma triacylglycerol levels and increased the heparin-induced release of lipoprotein lipase into the incubation medium of cardiac myocytes. The acute (3–5 days) induction of diabetes by streptozotocin (100 mg/kg) produced hypertriglyceridemia and reduced heparin-releasable lipoprotein lipase activity in cardiac myocytes. Treatment of diabetic rats with 4-aminopyrazolopyrimidine resulted in a fall in plasma triacylglycerol content and increased heparin-releasable lipoprotein lipase activity. Administration of Triton WR-1339 also resulted in hypertriglyceridemia, but the heparin-induced release of lipoprotein lipase from control cardiac myocytes was not reduced in the absence of lipolysis of triacylglycerol-rich lipoproteins. Treatment with Triton WR-1339 did, however, increase the heparin-induced release of lipoprotein lipase from diabetic cardiac myocytes. Preparation of cardiac myocytes with 0.9 mM oleic acid resulted in a decrease in both total cellular and heparin-releasable lipoprotein lipase activities. These results suggest that the diabetes-induced reduction in heart lipoprotein lipase activity may, at least in part, be due to an inhibitory effect of free fatty acids, derived either from lipoprotein degradation or from adipose tissue lipolysis, on lipoprotein lipase activity in (and (or) release from) cardiac myocytes.Key words: diabetes, plasma triacylglycerols, cardiac myocytes, lipoprotein lipase.

scholarly journals Forms of lipoprotein lipase in rat tissues: in adipose tissue the proportion of inactive lipase increases on fasting

1996 ◽  
Vol 313 (3) ◽  
pp. 893-898 ◽  
Author(s):  
Martin BERGÖ ◽  
Gunilla OLIVECRONA ◽  
Thomas OLIVECRONA
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Translational Regulation ◽  
Specific Activity ◽  
Catalytic Efficiency ◽  
Rat Tissues ◽  
Tissue Extracts ◽  
Significant Difference ◽  
Lpl Mass ◽  
Fasted Rats

Previous studies have shown that the ratio of lipoprotein lipase (LPL) catalytic activity to LPL mass in tissues differs in different conditions, but it is not clear whether this occurs by a change in the catalytic efficiency of the LPL molecules, or because of a shift in the relation between active and inactive forms of the enzyme. To explore this, we have measured LPL activity and mass in detergent extracts of rat tissues. LPL specific activity was high and similar in heart, skeletal muscle, lung and brain. The liver had significantly lower specific activity, which is in accord with previous findings that the liver takes up and catabolizes LPL. The specific activity was also low in adipose tissue from fasted rats. When tissue extracts were applied to columns of heparin–agarose and eluted by a gradient of NaCl, a peak of active LPL was eluted at 1.0 M NaCl, but there was also a peak of inactive LPL protein, which was eluted at 0.6 M NaCl. In adipose tissue, LPL activity decreased by 70–80% during an overnight fast, whereas LPL mass decreased by only 20–40%. The mass ratio between inactive and active LPL, as separated by heparin–agarose chromatography, increased from 0.5 to over 2 during the fast. In hearts there was no significant difference between fed and fasted rats in total LPL activity, LPL mass or in the distribution between inactive and active forms. The results indicate that the relation between inactive (probably monomeric) and active (dimeric) forms of LPL is a target for post-translational regulation in adipose tissue.

Purified postheparin plasma lipoprotein lipase in primary hyperlipoproteinemias

1975 ◽  
Vol 39 (6) ◽  
pp. 1022-1033 ◽  
Author(s):  
D. Ganesan ◽  
R. H. Bradford ◽  
G. Ganesan ◽  
W. J. McConathy ◽  
P. Alaupovic ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Specific Activity ◽  
Lipolytic Activity ◽  
Plasma Lipoprotein ◽  
Type I ◽  
Activity Type ◽  
Type Iii ◽  
Protein Peak ◽  
Enzyme Specific Activity ◽  
Hydrolysis Of

Purified postheparin plasma lipoprotein lipase (LPL) of normolipidemic and primary hyperlipoproteinemic subjects was characterized by lipoprotein C polypeptide activation and specificity for triglycerides in chylomicrons and VLDL. Chromatography of normal LPL on Sephadex G-100 resulted in two protein peaks, LPLC-1 (activated by C-I but not C-II) and LPLC-II (activated by C-II but not C-I). LPL from type I hyperlipoproteinemic subjects was not activated by C-I and C-II activation was reduced to 40% of control. Hydrolysis of chylomicron and VLDL triglycerides was severely impaired. Although chromatography of type I LPL resulted in two protein peaks, the protein peak corresponding to LPLC-I did not exhibit lipolytic activity and LPLC-II was reduced to 50% of control in protein and enzyme specific activity. Type III LPL was normal in respect to LPLC-I while LPLC-II averaged 40% of control. Hydrolysis of chylomicron and VLDL was reduced to 50% and 10% of control, respectively. An etiological implication for LPLC-I and/or LPLC-II in type I and III hyperlipoproteinemias is suggested.

Myocardial lipoprotein lipase activity: regulation by diabetes and fructose-induced hypertriglyceridemia

1995 ◽  
Vol 73 (3) ◽  
pp. 369-377 ◽  
Author(s):  
Limin Liu ◽  
David L. Severson
Keyword(s):  
Lipoprotein Lipase ◽  
Selective Reduction ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Compensatory Response ◽  
Perfusion Solution ◽  
Rat Hearts ◽  
Perfused Hearts ◽  
Control Plasma ◽  
Sustained Increase

The decrease in myocardial lipoprotein lipase (LPL) activity observed previously in acute, severe models of insulin-deficient diabetes may be a compensatory response to hypertriglyceridemia and a sustained increase in fatty acid delivery to cardiomyocytes. The administration of fructose (10% solution in the drinking water for 4 days) to rats produced hypertriglyceridemia, but heparin-releasable LPL activity from perfused hearts and total and heparin-releasable LPL activities in isolated cardiomyocytes were not reduced. The acute (4 day) induction of a mild diabetic state (60 mg/kg streptozotocin) resulted in modest hypertriglyceridemia, and a selective decrease in heparin-releasable LPL activity in perfused hearts; LPL activity in cardiomyocytes from diabetic rat hearts was not reduced. Therefore, the diabetes-induced fall in myocardial LPL activity is not secondary to hypertriglyceridemia, since fructose treatment did not change LPL activity. Perfusion of rat hearts with 100 μM lysophosphatidylcholine (LPC) released a small amount of LPL activity into the perfusate, but only if albumin was omitted from the perfusion solution. Thus, the selective reduction in heparin-releasable LPL activity in perfused diabetic hearts is probably not the consequence of displacement by LPC, a lipolytic product of the LPL-catalyzed degradation of triacylglycerol-rich lipoproteins. Circulating LPL activity in the plasma of diabetic rats was not decreased relative to control plasma enzyme activity; therefore, the reduction in heparin-releasable LPL activity is not because circulating LPL was less available for uptake by the endothelium in diabetic hearts.Key words: diabetes, lipoprotein lipase, perfused hearts, cardiomyocytes.

Alterations of lipolysis and lipoprotein lipase in chronically nicotine-treated rats

1996 ◽  
Vol 270 (2) ◽  
pp. E215-E223 ◽  
Author(s):  
C. Sztalryd ◽  
J. Hamilton ◽  
B. A. Horwitz ◽  
P. Johnson ◽  
F. B. Kraemer
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Hormone Sensitive Lipase ◽  
Mrna Levels ◽  
Cellular Mechanisms ◽  
Fed State ◽  
Epididymal Fat ◽  
Hormone Sensitive ◽  
Lpl Mass ◽  
Fat Pads

These studies examined the cellular mechanisms for lower adiposity seen with nicotine ingestion. Rats were infused with nicotine or saline for 1 wk and adipocytes isolated from epididymal fat pads. Nicotine-infused rats gained 37% less weight and had 21% smaller fat pads. Basal lipolysis was 78% higher, whereas the maximal lipolytic response to isoproterenol was blunted in adipocytes from nicotine-infused rats. The antilipolytic actions of adenosine and the levels of serum catecholamines were unaffected by nicotine. The nicotine-induced alteration in lipolysis was not associated with any changes in hormone-sensitive lipase. Nicotine caused a 30% decrease in lipoprotein lipase (LPL) activity, without any changes in LPL mass or mRNA levels, in epididymal fat in the fed state. In contrast, LPL activity, mass, and mRNA levels in heart were increased by nicotine whether animals were fed or fasted. These studies provide evidence for multiple mechanistic events underlying nicotine-induced alterations in weight and suggest that nicotine diverts fat storage away from adipose tissue and toward utilization by muscle.

scholarly journals Developmental regulation of the alpha-mannosidase gene in Dictyostelium discoideum: control is at the level of transcription and is affected by cell density.

1991 ◽  
Vol 11 (6) ◽  
pp. 3339-3347 ◽  
Author(s):  
J Schatzle ◽  
A Rathi ◽  
M Clarke ◽  
J A Cardelli
Keyword(s):  
Cell Density ◽  
Dictyostelium Discoideum ◽  
High Cell Density ◽  
Specific Activity ◽  
Developmental Regulation ◽  
Cdna Probe ◽  
Mrna Levels ◽  
High Cell ◽  
Enzyme Specific Activity ◽  
Negative Mutant

In Dictyostelium discoideum, there is a group of genes that are expressed following starvation and when exponentially growing cells reach high densities. We have examined the expression of one of these genes, alpha-mannosidase. Using an alpha-mannosidase cDNA probe in Northern (RNA) blot analysis, we have shown that the previously observed increase in alpha-mannosidase enzyme-specific activity during development is due to an increase in the levels of alpha-mannosidase mRNA. mRNA levels reach a maximum by 8 h of development and then begin to decline by 14 to 22 h. Using nuclear run-on analysis, we have found that this gene is regulated at the level of transcription. We also examined the effects of cell-cell contacts, cyclic AMP levels, and protein synthesis on expression of this gene and found that they were not critical in regulating its expression. However, cell density did play a major role in the expression of alpha-mannosidase. High cell density or the presence of buffer conditioned by high-density cells was sufficient to induce expression of alpha-mannosidase, indicating that this is one of the prestarvation response genes. Finally, the alpha-mannosidase gene was not expressed in aggregation-negative mutant strain HMW 404.

Peroxisome proliferator-activated receptor-α ligands inhibit cardiac lipoprotein lipase activity

2001 ◽  
Vol 281 (2) ◽  
pp. H888-H894 ◽  
Author(s):  
Rogayah Carroll ◽  
David L. Severson
Keyword(s):  
Lipoprotein Lipase ◽  
Specific Activity ◽  
Inhibitory Effect ◽  
Enzyme Synthesis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adult Rat ◽  
Similar Inhibitory Effect ◽  
Peroxisome Proliferator Activated Receptors ◽  
Cultured Cardiomyocytes

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate gene expression of lipoprotein lipase (LPL) in liver and adipose tissue. We examined the direct effect of PPAR-α ligands on LPL catalytic activity in cultured cardiomyocytes from adult rat heart. After overnight culture (16 h), 1 μM Wy-14643 and 10 μM BM-17.0744 decreased total cellular LPL activity to ∼50% of control with no change in enzyme synthesis or mass; as a consequence, PPAR-α activation produced a significant decrease in LPL specific activity (mU/ng LPL protein). Wy-14643 and BM-17.0744 also reduced heparin-releasable LPL activity and mass in the culture medium. Inhibition of LPL activity by Wy-14643 did not reduce the ability of insulin plus dexamethasone to stimulate cellular and heparin-releasable LPL activities. A similar inhibitory effect on cellular and heparin-releasable LPL activity was observed when cardiomyocytes were cultured with 60 μM linoleic acid. In conclusion, two different PPAR-α ligands (Wy-14643 and BM-17.0744) inhibited cellular LPL activity in cultured cardiomyocytes by a posttranscriptional and posttranslational mechanism.

scholarly journals Tissue-specific activity of lipoprotein lipase in skeletal muscle regulates the expression of uncoupling protein 3 in transgenic mouse models

2001 ◽  
Vol 355 (3) ◽  
pp. 647-652 ◽  
Author(s):  
Dagmar KRATKY ◽  
Juliane G. STRAUSS ◽  
Rudolf ZECHNER
Keyword(s):  
Skeletal Muscle ◽  
Lipoprotein Lipase ◽  
Specific Activity ◽  
Uncoupling Protein ◽  
Large Body ◽  
Mrna Levels ◽  
Expression Levels ◽  
Uncoupling Protein 3 ◽  
Triacylglycerol Hydrolysis ◽  
Brown Adipose

Uncoupling protein (UCP)-2 and UCP-3 are two recently discovered proteins similar to UCP-1, which regulates thermogenesis in brown adipose tissue (BAT). Whereas UCP-1 expression is restricted to BAT, UCP-2 is widely expressed. UCP-3 is found mainly in skeletal muscle and BAT. A large body of evidence exists that the expression of UCP-2 and UCP-3 in skeletal muscle of mice is regulated by feeding/fasting, and some studies have suggested that this effect might be caused by the changing concentration of plasma non-esterified fatty acids (NEFAs). In an attempt to determine whether the increased import of triacylglycerol-derived NEFAs can also affect UCP expression, we determined the mRNA levels of UCP-1, UCP-2 and UCP-3 in BAT and muscle of induced mutant mouse lines that overexpressed or lacked lipoprotein lipase (LPL) in these tissues. The expression levels of UCP-1 and UCP-2 in BAT and in skeletal and cardiac muscle respectively were not affected by variations in tissue LPL activities. In contrast, UCP-3 mRNA levels were induced 3.4-fold in mice with high levels of LPL in skeletal muscle, and down-regulated in mice that lacked LPL in skeletal muscle. The presence or absence of LPL in BAT had no effect on UCP-3 expression levels. The response of UCP-3 mRNA expression to variations in LPL activity in skeletal muscle was independent of the feeding status or of plasma NEFA concentrations. These findings indicated that NEFAs as lipolytic products of LPL-mediated triacylglycerol hydrolysis markedly affect UCP-3 expression and that increased LPL activities occurring during fasting in skeletal muscle contribute to the induction of UCP-3 expression by promoting the increased uptake of NEFAs. In addition, our results demonstrate that UCP-2 and UCP-3 are differentially regulated in response to LPL-mediated NEFA uptake in skeletal muscle of mice.

Developmental regulation of the alpha-mannosidase gene in Dictyostelium discoideum: control is at the level of transcription and is affected by cell density

1991 ◽  
Vol 11 (6) ◽  
pp. 3339-3347
Author(s):  
J Schatzle ◽  
A Rathi ◽  
M Clarke ◽  
J A Cardelli
Keyword(s):  
Cell Density ◽  
Dictyostelium Discoideum ◽  
High Cell Density ◽  
Specific Activity ◽  
Developmental Regulation ◽  
Cdna Probe ◽  
Mrna Levels ◽  
High Cell ◽  
Enzyme Specific Activity ◽  
Negative Mutant

In Dictyostelium discoideum, there is a group of genes that are expressed following starvation and when exponentially growing cells reach high densities. We have examined the expression of one of these genes, alpha-mannosidase. Using an alpha-mannosidase cDNA probe in Northern (RNA) blot analysis, we have shown that the previously observed increase in alpha-mannosidase enzyme-specific activity during development is due to an increase in the levels of alpha-mannosidase mRNA. mRNA levels reach a maximum by 8 h of development and then begin to decline by 14 to 22 h. Using nuclear run-on analysis, we have found that this gene is regulated at the level of transcription. We also examined the effects of cell-cell contacts, cyclic AMP levels, and protein synthesis on expression of this gene and found that they were not critical in regulating its expression. However, cell density did play a major role in the expression of alpha-mannosidase. High cell density or the presence of buffer conditioned by high-density cells was sufficient to induce expression of alpha-mannosidase, indicating that this is one of the prestarvation response genes. Finally, the alpha-mannosidase gene was not expressed in aggregation-negative mutant strain HMW 404.

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