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Abstract

BackgroundLipoprotein lipase (LPL) is anchored at the vascular endothelium through interaction with heparan sulfate. It is not known how this enzyme is turned over but it has been suggested that it is slowly released into blood and then taken up and degraded in the liver. Heparin releases the enzyme into the circulating blood. Several lines of evidence indicate that this leads to accelerated flux of LPL to the liver and a temporary depletion of the enzyme in peripheral tissues.ResultsRat livers were found to contain substantial amounts of LPL, most of which was catalytically inactive. After injection of heparin, LPL mass in liver increased for at least an hour. LPL activity also increased, but not in proportion to mass, indicating that the lipase soon lost its activity after being bound/taken up in the liver. To further study the uptake, bovine LPL was labeled with 125I and injected. Already two min after injection about 33 % of the injected lipase was in the liver where it initially located along sinusoids. With time the immunostaining shifted to the hepatocytes, became granular and then faded, indicating internalization and degradation. When heparin was injected before the lipase, the initial immunostaining along sinusoids was weaker, whereas staining over Kupffer cells was enhanced. When the lipase was converted to inactive before injection, the fraction taken up in the liver increased and the lipase located mainly to the Kupffer cells.ConclusionsThis study shows that there are heparin-insensitive binding sites for LPL on both hepatocytes and Kupffer cells. The latter may be the same sites as those that mediate uptake of inactive LPL. The results support the hypothesis that turnover of endothelial LPL occurs in part by transport to and degradation in the liver, and that this transport is accelerated after injection of heparin.

Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome

“…3a), suggesting that circulating Angptl4 levels underestimated the total Angptl4 production and effect in nephrotic syndrome. Whereas normal rats degrade Angptl4-released LPL by hepatic uptake from the circulation 17 , we observed additional loss in the urine in nephrotic syndrome (Supplementary Fig. 3b,c).…”

Transgenic Expression and Genetic Variation of Lmf1 Affect LPL Activity in Mice and Humans

“…However, the fate of extracellular LPL is tissue context-dependent and determined in large part by the expression of angiopoietin-like protein 4 (Angptl4), which dissociates and inactivates the LPL dimer, 32 and the turnover rate of inactive LPL as a function of tissue perfusion and hepatic degradation. 33 Consistent with such tissue-specific differences, LPL specific activity was found to be highly variable between human adipose depots and adipose vs heart tissue in the mouse. 34, 35 In conclusion, LPL mass and specific activity in a given tissue are subject to the effects of intra- and extracellular biosynthetic and degradation pathways and the apparent variability in our transgenic models is a likely reflection of this complexity.…”

Cardiac lipoprotein lipase activity in the hypertrophied heart may be regulated by fatty acid flux

“…Given the continual utilisation of LPL and the loss from the endothelial surface of capillaries with the recycling of LPL with remnant lipoprotein particles this mechanism may show a degree of auto-regulation [27]. Both TAG and cholesterol accumulation in the liver following Western diet may be indicative of such remnant particle recovery [28]. However the determinants for the frequency of LPL replacement at the endothelium are unclear, one such trigger is the activation of AMPK by synthetic agents such as AICAR or perhexiline [29], metformin [8] or ischemia-reperfusion injury [30].…”