Disease relevance of Lipc

• Post-heparin hepatic lipase activity is reduced in chronic renal failure (CRF) [1].
• Accelerated lipoprotein uptake by transplantable hepatomas that express hepatic lipase [2].
• Hypoxia and dexamethasone treatment each decreased total hepatic lipase activity [3].
• The differential effect of PTx on HL and LPL on the one hand and VLDL-R on the other can, in part, account for partial as opposed to complete correction of the associated hypertriglyceridemia with PTx in the CRF animals [4].
• Several features of the nephrotic dyslipidemia point to the possible presence of HL deficiency [5].

High impact information on Lipc

• Culture of hepatic cells for 8 h was associated with an increase in hepatic lipase activity but the increment in CRF rats was significantly (P < 0.01) lower than that of normal, CRF-PTX, CRF-V, and normal-V rats [1].
• Infusion of heparin to the in vitro hepatic perfusion system increased the activity of hepatic lipase in the effluent in all groups of rat except in CRF animals [1].
• Both parathyroid hormone (PTH)-(1-84) and 1-34 inhibited the production of hepatic lipase in cultured cells from normal, CRF-PTX, CRF-V, and normal-V rats [1].
• We examined hepatic lipase metabolism in normal, 6-wk-old CRF rats, CRF-PTX (parathyroidectomized) rats, and CRF and normal rats treated with verapamil (CRF-V, normal-V) using liver homogenate, hepatic cell culture for 8 h, and in vitro liver perfusion [1].
• Heparin-releasable plasma lipoprotein lipase and hepatic lipase activities were decreased by 50% in nephrotic rats compared with pair-fed controls [6].

Chemical compound and disease context of Lipc

• In an attempt to address this possibility, gene expression of HL was studied in rats with puromycin-induced nephrotic syndrome (NS) [5].
• No differences between the TPN groups were observed concerning liver steatosis, cholesterol metabolism, phospholipid metabolism or HL activity [7].
• These data indicate that at least part of the decrease of HL activity during hypothyroidism is due to the concomitant GH deficiency, and that GH rather than thyroid hormone may regulate HL mRNA levels [8].
• The mechanism for the stimulation of hepatic lipase secretion by heparin was studied in cultured Fu5AH rat hepatoma cells [9].
• Cyclic AMP might be involved in ethanol-induced fatty liver, since it activates hepatic lipase and might also participate in the fatty acid oxidation [10].

Biological context of Lipc

• Clones for rat hepatic lipase were isolated by probing a rat liver cDNA library in lambda gt11 with an oligonucleotide synthesized on the basis of a partial peptide sequence [11].
• Isolation and characterization of clones for the rat hepatic lipase gene upstream regulatory region [12].
• Genomic clones for 2287 nucleotides of the 5' flanking region, 135 nucleotides of the first exon, and 283 nucleotides of the first intron of the hepatic lipase gene were characterized [12].
• The results show that about two-thirds of plasma PLPC disappearance is due to phospholipase A1 hydrolysis, probably hepatic lipase [13].
• Amino acid sequence homology to serine proteases, thioesterases and other lipases, identified Ser147 of rat HL as part of a highly conserved element in an esterase gene family [14].

Anatomical context of Lipc

• The homologous mRNA is present in liver tissue but no detectable mRNA is observed in the adrenal gland, despite the reported presence of hepatic lipase in both the liver and the adrenal gland [11].
• HL is synthesized in hepatocytes and functions while bound to heparan sulfate proteoglycans (HSPGs) in sinusoidal endothelial cells [15].
• Instead, hepatic lipase originating elsewhere, presumably in the liver, is accumulated from the circulation at heparin-sensitive sites in ovarian blood vessels [16].
• Hepatic lipase, a glycoprotein synthesized and secreted by the hepatocyte, binds to sinusoidal endothelium where it is involved in metabolism of lipoprotein phospholipid and triglyceride [17].
• Following injection of Xenopus oocytes with SP6 transcripts for normal or mutant HL, media from the oocytes were assayed for lipolytic activity and immunoprecipitable HL protein [14].

Associations of Lipc with chemical compounds

• Moreover, plasma HDL cholesterol and hepatic lipase activity were closely associated with low aortic cholesterol and triacylglycerol in rats fed polymeric tannins [18].
• After heparin administration in vivo, hepatic lipase activity in plasma increased nearly 100-fold with appearance of an additional 55 kDa band in postheparin plasma [19].
• CHO-TPN increased the uptake of a radiolabeled triglyceride emulsion and increased hepatic lipase activity, whereas Lipid-TPN decreased both [20].
• The activation of triacylglycerol hydrolysis was not due to altered penetration of HL [21].
• Glucose trimming of HL protein was not affected by CCCP, as indicated by digestion of immunoprecipitates with jack bean alpha-mannosidase [22].

Physical interactions of Lipc

• Removal of chylomicron remnants by the liver involves interaction with several macromolecules on the cell surface, including the LDL receptor and heparan-sulfate-bound hepatic lipase and apolipoprotein E [23].

Enzymatic interactions of Lipc

• Activation of hepatic lipase catalyzed phosphatidylcholine hydrolysis by apolipoprotein E [24].

Regulatory relationships of Lipc

• Secretion of rat hepatic lipase is blocked by inhibition of oligosaccharide processing at the stage of glucosidase I [25].
• At d 28 of protein malnutrition, plasma total lipolytic activities were significantly reduced in both depleted groups, (P < 0.05); hepatic lipase values represented 23% of the control value and lipoprotein lipase activity was about 11% of the control value [26].
• Hepatic lipase catalyzed phospholipid hydrolysis was 1.8-fold activated by apolipoprotein E while the other apolipoproteins did not affect the hydrolysis by this enzyme [24].
• We have found that release of hepatic lipase activity is stimulated from liver slices by epidermal growth factor (EGF) into the medium in a time-dependent manner [27].

Other interactions of Lipc

• The effects of monomeric and polymeric grape seed tannins on rat plasma lipoproteins, lipoprotein lipase, hepatic lipase and aortic and hepatic lipid concentration were studied [18].
• Sequence polymorphisms detected between the BN and GK strains in genes encoding ApoAI, AIV, CIII and Lipc do not account for these effects [28].
• Abnormalities in hepatic lipase in chronic renal failure: role of excess parathyroid hormone [1].
• From these findings it is concluded that large chylomicron remnants initially bind rapidly to surface components other than the LDL receptor, one of which may be hepatic lipase [29].
• Amino acid sequence homology analysis revealed that the enzyme shares about 30% homology with mammalian lipases (lipoprotein lipase, hepatic lipase, and pancreatic lipase) [30].

Analytical, diagnostic and therapeutic context of Lipc

• Real-time PCR and Northern blots demonstrated that PG production was significantly reduced in animals lacking HL [15].
• Confocal microscopy of liver sections showed that a modest amount of HL colocalized with chylomicron remnant clusters in the transgenic mice, suggesting that HL is a component of the LRP-proteoglycan clusters [31].
• Infusion of PTH-(1-34) in dose of 10(-6) M into the liver perfusion system inhibited the increase in post-heparin hepatic lipase activity [1].
• An intracellular 53,000-dalton precursor of the mature 59,000-dalton hepatic lipase was identified by immunoprecipitation [17].
• Similarly, hepatic lipase mRNA was detectable in liver but not ovaries or kidneys by Northern or slot blot analyses or by the polymerase chain reaction [16].

References