Nutritional regulation of lipoprotein lipase in guinea pig tissues

Semb, Henrik; Olivecrona, Thomas

doi:10.1016/0005-2760(86)90281-x

Cited by 58 publications

(33 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We did not explore whether the stabilizing effect of VLDL was due to direct interaction with LPL or possibly to generation of small amounts of lipolytic products (such as free fatty acids and glycerol) during the long times required for refolding. Detergents (such as Triton X-100, SDS, and deoxycholate) and long chain fatty acids have previously been shown to increase the solubility and stability of LPL (40). Fig.…”

Section: Discussionmentioning

confidence: 99%

Calcium Triggers Folding of Lipoprotein Lipase into Active Dimers

Zhang

Lóokene

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

The active form of lipoprotein lipase (LPL) is a noncovalent homodimer of 55-kDa subunits. The dimer is unstable and tends to undergo irreversible dissociation into inactive monomers. We noted that a preparation of such monomers slowly regained traces of activity under assay conditions with substrate, heparin, and serum or in cell culture medium containing serum. We therefore studied the refolding pathway of LPL after full denaturation in 6 M guanidinium chloride or after dissociation into monomers in 1 M guanidinium chloride. In crude systems, we identified serum as the factor promoting reactivation. Further investigations demonstrated that Ca 2؉ was the crucial component in serum for reactivation of LPL and that refolding involved at least two steps. Studies of far-UV circular dichroism, fluorescence, and proteolytic cleavage patterns showed that LPL started to refold from the C-terminal domain, independent of calcium. The first step was rapid and resulted in formation of an inactive monomer with a completely folded C-terminal domain, whereas the N-terminal domain was in the molten globule state. The second step was promoted by Ca 2؉ and converted LPL monomers from the molten globule state to dimerization-competent and more tightly folded monomers that rapidly formed active LPL dimers. The second step was slow, and it appears that proline isomerization (rather than dimerization as such) is rate-limiting. Inactive monomers isolated from human tissue recovered activity under the influence of Ca 2؉ . We speculate that Ca 2؉ -dependent control of LPL dimerization might be involved in the normal post-translational regulation of LPL activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Calcium Triggers Folding of Lipoprotein Lipase into Active Dimers

Zhang

Lóokene

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…21,30 The fasting-induced changes in cardiac LPL activity were suggested to be posttranslational and did not involve altered mRNA levels, protein synthesis, or specific activity of the protein. 11 As previously reported with the modified Langendorff perfused heart, 18 the fastinginduced increase in heparin-releasable LPL activity occurred mainly at the coronary lumen.…”

Section: Figurementioning

confidence: 99%

Localization of Lipoprotein Lipase in the Diabetic Heart

Sambandam

Abrahani

Pierre

et al. 1999

ATVB

View full text Add to dashboard Cite

Abstract-Vascular endothelium-bound lipoprotein lipase (LPL) is rate limiting for free fatty acid (FFA) transport into tissues. In streptozotocin (STZ)-diabetic rats, we have previously demonstrated an increased heparin-releasable LPL activity from perfused hearts. Because heparin can traverse the endothelial barrier, conventional Langendorff retrograde perfusion of the heart with heparin could release LPL from both the capillary luminal and abluminal surfaces. To determine the precise location of the augmented LPL, a modified Langendorff retrograde perfusion was used to isolate the enzyme at the coronary lumen from that in the interstitial effluent. In response to heparin, a 4-fold increase in LPL activity and protein mass was observed in the coronary perfusate after 2 weeks of STZ diabetes. Release of LPL activity into the interstitial fluid of control hearts was slow but progressive, whereas in diabetic hearts, peak enzyme activity was observed within 1 to 2 minutes after heparin, followed by a gradual decline. Immunohistochemical studies of myocardial sections confirmed that the augmented LPL in diabetic hearts was mainly localized at the capillary endothelium. To study the acute effects of insulin on endothelial LPL activity, we examined rat hearts at various times after the onset of hyperglycemia. An increased heparin-releasable LPL activity in diabetic rats was demonstrated shortly (6 to 24 hours) after STZ injection or after withdrawal from exogenous insulin. Heparin-releasable coronary LPL activity was also increased after an overnight fast. These studies indicate that the intravascular heparin-releasable fraction of cardiac LPL activity is acutely regulated by short-term changes in insulin rather than glucose. Thus, during short periods (hours) of hypoinsulinemia, increased LPL activity at the capillary endothelium can increase the delivery of FFAs to the heart. The resultant metabolic changes could induce the subsequent cardiomyopathy that is observed in the chronic diabetic rat.

show abstract

“…The adipose depot used in all experiments was the periepididymal one. In some experiments the tissue was cut into small pieces and digested with collagenase to isolate the adipocytes as described (19). The animal ethics committee in Umeå approved the animal experiments.…”

Section: Methodsmentioning

confidence: 99%

The Distribution of Lipoprotein Lipase in Rat Adipose Tissue

Olivecrona

2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Lipoprotein lipase (LPL) acts at the vascular endothelium. Earlier studies have shown that down-regulation of adipose tissue LPL during fasting is post-translational and involves a shift from active to inactive forms of the lipase. Studies in cell systems had indicated that during fasting LPL might be retained in the endoplasmic reticulum. We have now explored the relation between active/inactive and intra/extracellular forms of the lipase. Within adipocytes, neither LPL mass nor the distribution of LPL between active and inactive forms changed on fasting. Extracellular LPL mass also did not change significantly, but shifted from predominantly active to predominantly inactive. To explore if changes in secretion were compensated by changes in turnover, synthesis of new protein was blocked by cycloheximide. The rates at which intra-and extracellular LPL mass and activity decreased did not change on fasting. To further explore how LPL is distributed in the tissue, heparin (which detaches the enzyme from the endothelial surface) was injected. Tissue LPL activity decreased by about 10% in 2 min and by 50% in 1 h. Heparin released mainly the active form of the lipase. There was no change of LPL activity or mass within adipocytes. The fraction of extracellular LPL that heparin released and the time course were the same in fed and fasted rats, indicating that active, extracellular LPL was distributed in a similar way in the two nutritional states. This study suggests that the nutritional regulation of LPL in adipose tissue determines the activity state of extracellular LPL.

show abstract

Nutritional regulation of lipoprotein lipase in guinea pig tissues

Cited by 58 publications

References 24 publications

Calcium Triggers Folding of Lipoprotein Lipase into Active Dimers

Calcium Triggers Folding of Lipoprotein Lipase into Active Dimers

Localization of Lipoprotein Lipase in the Diabetic Heart

The Distribution of Lipoprotein Lipase in Rat Adipose Tissue

Contact Info

Product

Resources

About