Liver Lipase Research Articles

Relationship between lipoprotein lipase and peroxisome proliferator-activated receptor-α expression in rat liver during development

The present study was addressed to determine whether the high expression of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in rat liver during the perinatal stage plays a role in the induction of liver lipoprotein lipase (LPL) expression and activity. Parallel increases in liver mRNA PPAR-alpha and LPL activity were found in newborn rats, and after a slight decline, values remained elevated until weaning. Anticipated weaning for 3 days caused a decline in those two variables as well as in the mRNA LPL level, and a similar change was also found in liver triacylglycerol concentration. Force-feeding with Intralipid in 10-day-old rats or animals kept fasted for 5 h showed high mRNA-PPARalpha and -LPL levels as well as LPL activity with low plasma insulin and high FFA levels, whereas glucose and a combination of glucose and Intralipid produced low mRNA-PPARalpha and -LPL levels as well as LPL activity. Under these latter conditions, plasma insulin and FFA levels were high in those rats receiving the combination of glucose and Intralipid, whereas plasma FFA levels were low in those force-fed with glucose. It is proposed that the hormonal and nutritional induction of liver PPAR-alpha expression around birth and its maintained elevated level throughout suckling is responsible for the induction of liver LPL-expression and activity during suckling.

Replacing dietary fish oil by vegetable oils has little effect on lipogenesis, lipid transport and tissue lipid uptake in rainbow trout (Oncorhynchus mykiss)

In order to investigate the effects of dietary lipid sources on mechanisms involved in lipid deposition, two groups of rainbow trout were fed from first-feeding to the commercial size of 1 kg (for 62 weeks) with two diets differing only by lipid source: 100% fish oil or 100% blend of vegetable oils (55% rapeseed oil, 30% palm oil, 15% linseed oil). The activities and levels of gene expression of lipogenic enzymes (fatty acid synthetase, glucose-6-phosphate dehydrogenase and malic enzyme) in liver and of lipoprotein lipase in perivisceral adipose tissue, white muscle and liver were determined. Transport of lipid was studied by determining lipid composition of plasma and lipoprotein classes. We also examined the clearance of LDL by assaying the level of LDL receptor gene expression in several tissues. Total replacement of dietary fish oil by the blend of vegetable oils did not affect growth of rainbow trout and did not modify muscle lipid content. Hepatic lipogenesis and lipid uptake in perivisceral adipose tissue, white muscle and liver were also not modified by dietary treatments. Diets containing the blend of vegetable oils induced a decrease in plasma cholesterol and LDL. In trout fed the vegetable oils diet, expression of LDL receptor gene in the liver was down-regulated.

Replacement of a large portion of fish oil by vegetable oils does not affect lipogenesis, lipid transport and tissue lipid uptake in European seabass ( Dicentrarchus labrax L.)

In order to investigate the impact of dietary lipid sources on mechanisms involved in lipid deposition, three groups of European seabass fingerlings with average initial body weight of 5.2 ± 1.0 g were fed three diets differing only by lipid source. These diets were: 100% anchovy oil (diet A), 40% anchovy oil–60% mix of vegetable oils (35% linseed, 15% palm, 10% rapeseed) (diet B) and 40% anchovy oil–60% mix of vegetable oils (24% linseed, 12% palm, 24% rapeseed) (diet C). After 64 weeks of rearing, when seabass reached the size of 160 g, the activity of lipogenic enzymes (fatty acid synthetase, glucose-6-phosphate dehydrogenase and malic enzyme) in liver and of lipoprotein lipase (LPL) in perivisceral adipose tissue, liver and white muscle were measured. Transport of lipid by lipoproteins was examined by determining plasma lipid composition and lipoprotein classes. Dietary oil source did not modify growth performance or lipid content of flesh and liver of seabass. Replacement of 60% of fish oil by the two mixtures of vegetable oils had no significant effect on hepatic lipogenesis and activity of LPL in liver and adipose tissue. Activity of LPL in white muscle was decreased in fish fed diet C compared to those fed diets A and B. Diets containing the mixture of vegetable oils led to lowered plasma, VLDL and LDL cholesterol levels compared to diet A. It is concluded that replacing 60% of fish oil by the two mixtures of vegetable oils in the feeds of European seabass fingerlings until they reach the size of 160 g has no marked effect on growth performance, lipogenesis and tissue lipid uptake but has a hypocholesterolemic effect.

Effect of season and fishing ground on the activity of lipases in byproducts from cod ( Gadus morhua)

Lipase activity at acid and neutral pH has been measured in cut off, liver and viscera from cod caught in the Icelandic Sea (three different seasons) and the Barents Sea (one season). Lipase activity at pH 5 was highest in liver, while at pH 7 lipase activity was highest in viscera. Activity at pH 7 was higher than at pH 5 in liver and viscera, and at the same level in cut off. Lipase activity at pH 5 and 7 (20 °C) was higher in cut off samples from the Icelandic Sea in May–June, compared to October–December. Lipase activity at pH 7 (20 °C) was higher in cut off from the Barents Sea compared to the Icelandic Sea. No significant effect of season or fishing ground was found for liver lipase. Lipase activity at pH 5 and 7 in viscera from the Icelandic Sea was lower in May–June compared to the other seasons. Lipase activity was generally higher in viscera from the Icelandic Sea compared to the Barents Sea.

Effects of peripheral ghrelin on the carbohydrate and lipid metabolism of the tundra vole ( Microtus oeconomus)

Ghrelin is a novel orexigenic peptide hormone. In humans and rodents, it increases food intake and its levels are reduced in obesity but increased in fasting. It is an antagonistic signal to leptin informing the central nervous system about negative energy balance. The tundra vole ( Microtus oeconomus) is an interesting model to study the effects of ghrelin, as it is poorly adapted to fasting. In this study, 10 male voles were injected with intraperitoneal ghrelin at 10 μg kg −1 day −1 for four days, while 10 males received sham injections. Additional five males were food deprived for 4 h with five males as fed controls. Exogenous ghrelin caused an expected elevation in the plasma ghrelin concentrations. Furthermore, the plasma glucose and high density lipoprotein cholesterol concentrations increased but the kidney and muscle glycogen contents decreased. The liver lipase and kidney glycogen phosphorylase activities increased at the same time. Food deprivation caused an increase in the plasma ghrelin concentrations. In voles, ghrelin may be a mediator to recruit body energy reserves during negative energy balance that would be detrimental to voles very rapidly if foraging does not prove to be successful.

Reproduction of the tundra vole ( Microtus oeconomus) with dietary phytosterol supplement

Phytosterols (PS) are plant-derived compounds with estrogenic activity in vitro and beneficial effects on the serum lipid profile in vivo. In nature, PS exposure can derive from pulp mill effluents. The effects of a pulp-mill derived PS mixture on the reproduction, endocrine variables and enzyme activities of the tundra vole ( Microtus oeconomus) were investigated in a two-generation study. The cumulative food intake of PS-treated females was higher than in the control group supporting previous results on the effects of PS on food consumption in rodents. 85% of the PS treated pairs reproduced, but the figure was only 60% for the control pairs. The plasma and testicular testosterone concentrations were lower in the adult PS males, but the PS-treated male offspring had higher testicular testosterone concentrations than their controls. In the female offspring, the liver lipase activity was higher in the PS-treated group, which could be a result of decreased cholesterol absorption in the gut. Chronic PS treatment increased the reproduction probability of the species and had a potential effect on the sex steroid hormones of maturing offspring, which could have applications in environmental monitoring.

Effects of heparin on the uptake of lipoprotein lipase in rat liver

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.

Inactive hepatic lipase in rat plasma

Hepatic lipase activity is detectable in liver but also in adrenal glands, ovaries, and plasma. The subunit size of hepatic lipase in liver, adrenal glands, and nonheparin plasma was compared. Hepatic lipase in liver and adrenal glands appeared as a 55 kDa band. In liver, a faint band of lower size was also detected. In nonheparin plasma, hepatic lipase appeared as a doublet of 57 kDa and 59 kDa. When activity/mass ratio was calculated, similar values were obtained for liver and adrenal glands. In plasma this value was much lower. 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. This band coeluted with activity after preparative polyacrylamide gel electrophoresis. Differences in size persisted after digestion with peptide-N-glycosidase F. A progressive increase in 57 kDa and 59 kDa in postheparin plasma followed disappearance of the 55 kDa band, suggesting that these larger bands originate from the smaller form. In plasma, both smaller and larger forms were associated with HDL, but not with LDL or VLDL. We conclude that rat plasma contains a larger form of hepatic lipase that is inactive in in vitro assay.

Antidyslipidemic action of fenofibrate in dyslipidemic–diabetic hamster model

Fenofibrate is the ligand for PPARα subtype that mediates the action of its agonists’ in lipid metabolism. How fibrate exerts hypolipidemic effect? The mechanism is studied in a newly developed high-fat fructose enriched diet induced dyslipidemia–diabetic hamster model. Fenofibrate lowered the basal plasma lipids like TC, TG, PL, FFA, glycerol, VLDL, and LDL, but HDL was increased. The activity of lipoprotein lipase in liver, adipose tissue, and small intestine was upregulated. However, that of triglyceride lipase was downregulated in liver. It has also improved the insulin secretion and plasma glucose lowering, caused by impairment in insulin secretion due to high-fat load. The drug was found effective in reducing body weight and diet due to rise in leptin level. Fenofibrate also enhanced the fecal excretion of total lipids, cholic acid, and deoxycholic acid probably by the activation of 7α cholesterol hydroxylase enzyme. Thus, causing broad-spectrum lipid lowering along with inhibition of hepatic lipid biosynthesis and maintaining lipid–glucose homeostasis.

The therapeutic benefit of fenofibrate to tamoxifen induced non-alcoholic steatohepatiis (NASH) patients with breast cancer: From the aspect of the inhibition of estrogen synthesis in ovary by fenofibrate

Peroxisome proliferators-activated receptor alpha (PPAR a) play important roles in metabolism of lipids in liver. Bezaflbrate or fenofibrate, ligands for PPAR el, restore the estrogendeficient induced non-alcoholic steatohepatitis(NASH) in human or in rodents as we reported previously, but whether or not estrogen synthesis in ovary are influenced by [igands of PPAR c~ in normal mice are not clarified yet. We report here that fenofibrate induce the gene expression involved in hepatic fatty acid metabolism and inhibit the synthesis of estrogen in ovary. C57BL6/J female mice fed with various amount of fenofibrate for four weeks had reducing serum triglycerides and hepatomegaly without any steatosis. Northern blotting analysis of the ovary revealed that the mRNA expression of enzymes involved in steroidgenesis such as Cyp19, Cypl 1A, steroidogenic acute regulatory protein and high-density lipoprotein receptor were suppressed, but the mRNA expression of Cyp17 was induced. Consistent with the suppression of Cyp19 mRNA expression, the aromatase which is an essential enzyme for estrogen synthesis in ovary was dose-dependently inhibited. And the inhibition of the enzyme resulted in the decreasing the uterine size and bone mineral density. Furthermore, fenofibrate induced PPAR atarget gene which are importantly involved in hepatic fatty acid metabolism such as acyl.coA oxidase and lipoprotein lipase in liver. PPAR n null mice fed with fenofibrate showed neither of hepatomegaly, decreasing the uterine size nor inhibition of ovarian aromatase activity. These results demonstrate that fenofibrate inhibits ovarian estrogen synthesis with PPAR n dependently. Taking together with the data of tamoxifen induced NASH in breast cancer patients treated with fenofibrate or bezafibrate, these medicine may be very beneficial for the treatment of breast cancer patients with NASH.

Phytosterols Act as Endocrine and Metabolic Disruptors in the European Polecat (Mustela putorius)

Phytosterols or plant sterols (PS) are consumed as natural remedies and margarines by the general population in developed countries to lower elevated serum cholesterol levels. They are also present in high concentrations in pulp mill effluents. The aim of the study was to screen the endocrine and metabolic parameters of the European polecat (Mustela putorius) for the effects of PS. The results showed an increase in the plasma estradiol and TH levels with no effects on the hypophyseal regulatory hormones. The plasma ghrelin levels decreased. PS also affected intermediary metabolism. The liver glycogen content increased as did the kidney glucose-6-phosphatase activity. The liver lipase esterase activity, on the other hand, decreased due to PS. In serum lipids the total cholesterol did not change, but the low-density lipoprotein levels increased and the high-density lipoprotein–cholesterol ratio decreased. PS had widespread previously unreported effects on the physiology of the polecat. The multiple effects indicate the need of a thorough risk assessment of the effects and interactions of PS.

Peroxisome proliferator-activated receptor-alpha ligands inhibit cardiac lipoprotein lipase activity.

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-alpha ligands on LPL catalytic activity in cultured cardiomyocytes from adult rat heart. After overnight culture (16 h), 1 microM Wy-14643 and 10 microM BM-17.0744 decreased total cellular LPL activity to approximately 50% of control with no change in enzyme synthesis or mass; as a consequence, PPAR-alpha 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 microM linoleic acid. In conclusion, two different PPAR-alpha ligands (Wy-14643 and BM-17.0744) inhibited cellular LPL activity in cultured cardiomyocytes by a posttranscriptional and posttranslational mechanism.

Immunochemical localization of hepatic triglyceride lipase (HTGL) in human liver and its physiological role illustrated by analysis of dyslipoproteins in a subject with homozygous HTGL deficiency

Immunochemical localization of hepatic triglyceride lipase (HTGL) in human liver and its physiological role illustrated by analysis of dyslipoproteins in a subject with homozygous HTGL deficiency

Partial hepatectomy and/or surgical stress provoke changes in the expression of lipoprotein lipase and actin in liver and extrahepatic tissues

The expression of lipoprotein lipase (LPL) and actin genes was examined in heart, muscle and white adipose tissue (WAT) and the expression of albumin and actin genes was examined in regenerating liver after 2/3 hepatectomy. Both surgical stress and partial hepatectomy (PH) affected LPL and actin mRNA levels in muscle and WAT, but not in heart. The changes in LPL mRNA suggest transcriptional regulation of the enzyme during hepatic regeneration. Our results show for the first time that the LPL gene expression in the different tissues studied is altered not only by the surgical stress, but also by PH per se. Actin expression is also affected in some tissues. In liver, PH and surgical stress altered the expression of albumin and total mRNA. The total mRNA of the other tissues studied did not change. The changes observed in LPL in different tissues, especially in WAT and muscle, may be responsible for some of the changes in lipidic metabolism, thus allowing for some plasma lipoproteins to be used as substrates by the LPL activity that arises in the liver during hepatic regeneration. The fatty acids derived from these lipoproteins would constitute not only an energy source but also the building material needed in the process of restoration of the lost hepatic mass. It is suggested that hormonal changes taking place after surgery are responsible for the variation in the levels of the different mRNAs studied.

Cloning of a Unique Lipase from Endothelial Cells Extends the Lipase Gene Family

A new lipoprotein lipase-like gene has been cloned from endothelial cells through a subtraction methodology aimed at characterizing genes that are expressed with in vitro differentiation of this cell type. The conceptual endothelial cell-derived lipase protein contains 500 amino acids, including an 18-amino acid hydrophobic signal sequence, and is 44% identical to lipoprotein lipase and 41% identical to hepatic lipase. Comparison of primary sequence to that of lipoprotein and hepatic lipase reveals conservation of the serine, aspartic acid, and histidine catalytic residues as well as the 10 cysteine residues involved in disulfide bond formation. Expression was identified in cultured human umbilical vein endothelial cells, human coronary artery endothelial cells, and murine endothelial-like yolk sac cells by Northern blot. In addition, Northern blot and in situ hybridization analysis revealed expression of the endothelial-derived lipase in placenta, liver, lung, ovary, thyroid gland, and testis. A c-Myc-tagged protein secreted from transfected COS7 cells had phospholipase A1 activity but no triglyceride lipase activity. Its tissue-restricted pattern of expression and its ability to be expressed by endothelial cells, suggests that endothelial cell-derived lipase may have unique functions in lipoprotein metabolism and in vascular disease.

Total synthesis of R-(+)-patulolide A and R-(−)-patulolide B: The macrolides isolated from Penicillium urticae mutant

The title compounds (2E, 11R)-4-oxo-2-dodecen-11-olide, 1 and (2Z, 11R)-4-oxo-2-dodecen-11-olide, 2 were synthesised in optically pure forms from a nitroalkane synthon involving a chiral resolution step using goat liver lipase.

ChemInform Abstract: Goat Liver Lipase: An Efficient Biocatalyst for Enantioselective Transesterification of Secondary Alcohols Using Vinyl Acetate as Acyl Donor.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Chemoenzymic Synthesis of Optically Active 3‐Methyl‐ and 3‐ Butylphthalides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Goat Liver Lipase : An Efficient Biocatalyst for Enantioselective Transesterification of Secondary Alcohols using Vinyl Acetate as Acyl Donor

Goat Liver Lipase : An Efficient Biocatalyst for Enantioselective Transesterification of Secondary Alcohols using Vinyl Acetate as Acyl Donor

Functional molecular mass of rat hepatic lipase in liver, adrenal gland and ovary is different.

Lipoprotein lipase (LPL) is functionally active only as a dimer. It is also generally assumed that the highly homologous hepatic lipase functions as a dimer, but no clear evidence has been presented. A hepatic lipase-like activity, also indicated as L-type lipase, is present in adrenal and ovary tissues. This enzyme is thought to originate from the liver and to be identical to hepatic lipase. We determined the functional molecular mass of hepatic lipase in rat liver, adrenal gland and ovary by radiation inactivation, a method for determining the functional size of a protein without the need of prior purification. Samples were exposed to ionizing radiation at -135 degrees C. Hepatic lipase activity in liver homogenate showed a single exponential decay. The functional molecular mass was calculated to be 63 +/- 10 kDa. Hepatic lipase activity in adrenal homogenate was found to have a functional molecular mass of 117 +/- 16 kDa. The functional molecular masses of the lipases partially purified from rat liver perfusate, adrenal homogenate or ovarian homogenate showed the same pattern, a target mass for the liver enzyme of 56 +/- 6 kDa and a target mass of 117 +/- 14 kDa for the enzyme from adrenal gland or ovary. In Western blot analysis the mass of the structural units of hepatic lipase in liver was 57 kDa and in adrenal and ovary tissue 51 kDa. We conclude that the functional unit of hepatic lipase in the liver is a monomer. The enzyme in adrenal gland and ovary is different from the liver and the functional unit may be a dimer.