Heart Lipoprotein Lipase Activity Research Articles

Is endothelial lipase a supporting actor of lipoprotein lipase in obesity?

Aim: Lipoprotein lipase (LPL) and endothelial lipase (EL) are involved in lipoproteins metabolism. In insulin-resistant states (IR), with visceral adipose tissue (AT) expansion and cardiac steatosis, these enzymes behavior is altered. Peroxisome Proliferator Activated Receptors (PPARs) could be partly responsible of these alterations. Our aim was to evaluate LPL and EL activity in AT and heart, their association with lipoprotein profile and the role of PPARs expression in an obesity model.

Lipolysis, and not hepatic lipogenesis, is the primary modulator of triglyceride levels in streptozotocin-induced diabetic mice.

Diabetic hypertriglyceridemia is thought to be primarily driven by increased hepatic de novo lipogenesis. However, experiments in animal models indicated that insulin deficiency should decrease hepatic de novo lipogenesis and reduce plasma triglyceride levels. To address the discrepancy between human data and genetically altered mouse models, we investigated whether insulin-deficient diabetic mice had triglyceride changes that resemble those in diabetic humans. Streptozotocin-induced insulin deficiency increased plasma triglyceride levels in mice. Contrary to the mouse models with impaired hepatic insulin receptor signaling, insulin deficiency did not reduce hepatic triglyceride secretion and de novo lipogenesis-related gene expression. Diabetic mice had a marked decrease in postprandial triglycerides clearance, which was associated with decreased lipoprotein lipase and peroxisome proliferator-activated receptor α mRNA levels in peripheral tissues and decreased lipoprotein lipase activity in skeletal muscle, heart, and brown adipose tissue. Diabetic heterozygous lipoprotein lipase knockout mice had markedly elevated fasting plasma triglyceride levels and prolonged postprandial triglycerides clearance. Insulin deficiency causes hypertriglyceridemia by decreasing peripheral lipolysis and not by an increase in hepatic triglycerides production and secretion.

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

Cardiac hypertrophy is characterised by an imbalance between lipid uptake and fatty acid β-oxidation leading to an accumulation of lipids, particularly triacylglycerol (TAG). It is unclear whether uptake mechanisms such as lipoprotein lipase (LPL) can be attenuated to diminish this uptake. Rats were cold acclimated to induce cardiac hypertrophy and increase cardiac LPL. Lipid uptake and metabolism were altered by feeding a ‘Western-style’ high fat diet (WSD) or feeding oxfenicine (2g/L) in the drinking water. Diastolic stiffness (increased volume change/unit pressure change) was induced in hypertrophied hearts for rats fed WSD (P<0.05) or WSD+oxfenicine (P<0.01), although absolute performance of cardiac muscle, estimated from stress–strain calculations was unchanged. Cold acclimation increased cardiac endothelial LPL (P<0.05) but this was diminished following oxfenicine. Following WSD LPL was further decreased below WSD-fed control hearts (P<0.05) with no further decrease by oxfenicine supplementation. A negative correlation was noted between plasma TAG and endothelial LPL (correlation coefficient=−0.654; P<0.001) but not cardiac TAG concentration. Transcript levels of angiopoietin-like protein-4 (ANGPTL4) were increased 6-fold by WSD (P<0.05) and increased 15-fold following WSD+oxfenicine (P<0.001). For CA-hearts fed WSD or WSD+oxfenicine ANGPTL4 mRNA levels were preserved at chow-fed levels. VLDLR protein levels were increased 10-fold (P<0.01) by CA. ANGPTL4 protein levels were increased 2-fold (P<0.05) by WSD, but restored following oxfenicine. For CA-hearts WSD increased ANGPTL4 protein levels 3-fold (P<0.01) with WSD+oxfenicine increasing ANGPTL4 protein 4-fold (P<0.01). These data suggest that endothelial LPL levels in the heart are altered to maintain FA flux and may exploit ANGPTL4.

Acute Intermittent Hypoxia Inhibits Triglycerides Clearance And Has a Tissue‐Specific Effect on Lipoprotein Lipase Activity

Background We have recently shown that chronic intermittent hypoxia (IH) decreases triglycerides (TG) clearance due to the inhibition of lipoprotein lipase (LPL) activity in adipose tissue. However, the impact of acute IH on TG clearance and LpL activity remains unknown. Methods Male C57BL/6J mice were exposed to 7hs of IH with FiO2 decreasing from 20.9% to 5% once per minute or to intermittent air (IA). During the exposure, intralipid (20%, 7.5 ml/kg) was administered and serum triglyceride levels were measured over the 2 hr time course. In a separate batch of mice, fasting (5 hrs) LPL activity was measured in the epididymal fat pads, heart and skeletal muscle. Results Compared to IA, IH increased TG levels throughout the 2 hr time course of intralipid (p <0.01). Exposure to IH for 7 hrs resulted in a significant decrease in adipose LPL activity (IA: 5.83±0.51 vs. IH: 4.40±0.29 umol FFA released/g/hr; P<0.05) and a significant increase in the heart LPL activity (IA: 42.61±2.28 vs. IH: 60.70±3.05 umol FFA released/g/hr; P<0.01). No difference was observed in the skeletal muscle. Conclusions Acute IH inhibits TG clearance, possibly by suppressing adipose LpL activity. A simultaneous increase in heart LpL may be attributable to the heightened myocardial demand in fatty acids as a source of energy. Research Support: R01 HL80105, AHA 10GRNT3360001, 5P50HL084945, FAPESP 2010/11681-0

Purified chickpea or lentil proteins impair VLDL metabolism and lipoprotein lipase activity in epididymal fat, but not in muscle, compared to casein, in growing rats

It is well known that the legume proteins have a lowering effect on plasma cholesterol and triacylglycerols (TG) concentrations compared to animal proteins. The protein itself, as well as non-protein constituents, naturally present in legumes may be implicated. The effects of various dietary purified legumes proteins compared to casein, were determined on plasma TG level, VLDL concentration and composition. Moreover, lipoprotein lipase (LPL) activity in epididymal fat, gastrocnemius and heart was investigated to evaluate in these tissues their capacity to release free fatty acids from their TG substrate and the liver capacity to stock the TG. Weaning male Wistar rats were fed ad libitum one of the following diets: 200 g/kg diet of purified proteins of lentil (L), or chickpea (CP) or casein (CAS). At day 28, VLDL were isolated from plasma sample by a single ultracentrifugation flotation. Hepatic lipase and LPL activity in epididymal fat, gastrocnemius and heart were measured by using glycerol tri [9-10(n)-(3)H] oleate emulsion as substrate. Compared with CAS diet, the CP and L protein diets exhibited similar cholesterolemia, but lower triglyceridemia (1.9-fold and 2.5-fold) and VLDL particle number, as measured by their reduced contents of TG and apolipoproteins. CP and L protein diets reduced liver TG and cholesterol by 31 and 45%, respectively compared to CAS diet. Furthermore, LPL activity in adipose tissue of rats fed CP or L was 1.6-fold lower than that of rats fed CAS. There was no significant difference in heart and gastrocnemius LPL activities with the three proteins. In contrast, hepatic lipase activity was higher in rats fed CP and L diets. The low food efficiency ratio of purified CP and L proteins related to CAS is associated with decreased plasma VLDL and adipose tissue LPL activity. The low liver TG concomitant with reduced TG and apolipoproteins contents of VLDL confirm that hypotriglyceridemia is essentially due to impaired synthesis, exportation and transport of TG by VLDL which prevent lipid storage in adipose tissue.

Hepatic and Adipose Tissue Depot‐Specific Changes in Lipid Metabolism in Late‐Onset Obese (LOB) Rats

Transgenic Late-onset OBesity (LOB) rats slowly develop a male-specific, autosomal dominant, obesity phenotype with a specific increase in peri-renal white adipose tissue (WAT) depot and preserved insulin sensitivity (Bains et al. in Endocrinology 145:2666-2679, 2004). To better understand the remarkable phenotype of these rats, the lipid metabolism was investigated in male LOB and non-transgenic (NT) littermates. Total plasma cholesterol (C) levels were normal but total plasma triacylglycerol (TAG) (2.8-fold) and hepatic TAG content (25%) was elevated in LOB males. Plasma VLDL-C and VLDL-TAG levels were higher while plasma apoB levels were 60% lower in LOB males. Increased hepatic TAG secretion explained the increased VLDL levels in LOB males. The hepatic gene expression of FAS, SCD-1, mitochondrial (mt)GPAT, and DGAT2 was up-regulated in both old obese and young non-obese LOB rats. Lipoprotein lipase (LPL) activity in heart and epididymal white adipose tissue (WAT) was unchanged, while LPL activity was increased in peri-renal WAT (30%) and decreased in soleus muscle (40%). Moreover, FAS, SCD-1 and DGAT2 gene expression was increased in peri-renal, but not in epididymal WAT. Basal lipolysis was reduced or unchanged and beta-adrenergic stimulated lipolysis was reduced in WAT from both old obese and young non-obese LOB rats. To summarize, the obese phenotype of LOB male rats is associated with increased hepatic TAG production and secretion, a shift in LPL activity from skeletal muscle to WAT, reduced lipolytic response in WAT depots and a specific increase in expression of genes responsible for fatty acid and TAG synthesis in the peri-renal depot.

Effects of active component in Cichorii on lipid metabolism of rat with hypertriglyceridemia complicated by hyperuricemia and hyperglycemia

To observe the effect of active component in Cichorii (N3) on lipid metabolism of rat with hypertriglyceridemia complicated by hyperuricemia and hyperglycemia. Hypertriglyceridemia complicated by hyperuricemia and hyperglycemia was induced in rats by feeding a kind of feedstuff containing high fructose for 21 days. Then three different doses of N3 were administered continuously to the rats for 35 days. The effects of N3 on lipid metabolism were observed by determining the levels of serum triglyceride (TG), uric acid (UA), glucose (GLU) and free fatty acids (FFA) and the activities of fatty acid synthetase (FAS) and hepatic lipase (HL) from the liver and lipoprotein lipase (LPL) from the heart. Twenty-one days after feeding a high-fructose diet, the levels of serum UA, TG and GLU in the untreated group were significantly higher than those of the normal control group. Thirty-five days after administering N3, there was no statistical difference in serum TG and heart LPL activity between the untreated group and the normal control group, while liver FAS activity, serum FFA level and liver HL activity in the untreated group were significantly higher than those in the normal control group. Different doses of N3 treated rats all showed a decrease of TG, UA and GLU levels. N3 could decrease FAS activity and FFA level, and increase LPL and HL activities significantly. N3 in Cichorii may regulate the lipid metabolism of the rats with hypertriglyceridemia complicated by hyperuricemia and hyperglycemia by decreasing FAS activity and FFA level, and increasing LPL and HL activities.

A transcription-dependent mechanism, akin to that in adipose tissue, modulates lipoprotein lipase activity in rat heart

The enzyme lipoprotein lipase (LPL) releases fatty acids from lipoprotein triglycerides for use in cell metabolism. LPL activity is rapidly modulated in a tissue-specific manner. Recent studies have shown that in rat adipose tissue this occurs by a shift of extracellular LPL toward an inactive form catalyzed by an LPL-controlling protein whose expression changes in response to the nutritional state. To explore whether a similar mechanism operates in other tissues we injected actinomycin D to block transcription of the putative LPL controlling protein(s). When actinomycin was given to fed rats, heparin-releasable LPL activity increased by 160% in heart and by 150% in a skeletal muscle (soleus) in 6 h. Postheparin LPL activity in blood increased by about 200%. To assess the state of extracellular LPL we subjected the spontaneously released LPL in heart perfusates to chromatography on heparin-agarose, which separates the active and inactive forms of the lipase. The amount of lipase protein released remained relatively constant on changes in the nutritional state and/or blockade of transcription, but the distribution between the active and inactive forms changed. Less of the LPL protein was in the active form in perfusates from hearts from fed compared with fasted rats. When glucose was given to fasted rats the proportion of LPL protein in the active form decreased. Actinomycin D increased the proportion that was active, in accord with the hypothesis that the message for a rapidly turning over LPL-controlling protein was being removed.

Nutritional regulation of lipoprotein lipase in mice

Tissue-specific regulation of lipoprotein lipase (LPL) has been extensively studied in rats. The mouse is now the most used animal in lipoprotein research, and we have therefore explored the regulation of LPL in this species. In C57 black mice, fed ad libitum adipose tissue LPL activity changed about three-fold with the time of day, indicating a circadian rhythm. The highest activity was at midnight and the lowest activity was at noon. Withdrawal of food did not markedly accelerate the drop of activity that occurred from midnight until noon, but prevented the return of activity that occurred during the evening and early night. When food was returned to mice that had been fasted for 24 h, adipose tissue LPL activity rose rapidly and returned to the fed level in 2 h. LPL mass in adipose tissue changed less than LPL activity, indicating that regulation is mainly post-translational as previously demonstrated for rats. When transcription was blocked in fasted mice, adipose tissue LPL activity increased, as previously observed in rats. LPL activity in heart was highest early in the light period at 9:00 h and lowest at 21:00 h. The change was, however, only about 30%. Heparin-releasable LPL activity in heart was 1.8-fold higher in mice fasted for 6 h compared to fed controls. We conclude that LPL activity responds to the nutritional state in the same direction and by the same mechanisms in mice as in rats, but the magnitude of the changes are less in mice.

Very Low Density Lipoprotein (VLDL) Receptor-deficient Mice Have Reduced Lipoprotein Lipase Activity: POSSIBLE CAUSES OF HYPERTRIGLYCERIDEMIA AND REDUCED BODY MASS WITH VLDL RECEPTOR DEFICIENCY

Although very low density lipoprotein (VLDL) receptor (VLDLr) knockout mice have been reported to have no lipoprotein abnormalities, they develop less adipose tissue than control mice when fed a high calorie diet. Mice that are deficient in adipose tissue expression of lipoprotein lipase (LpL) also have less fat, but only when crossed with ob/ob mice. We hypothesized that the VLDLr, a protein that will bind and transport LpL, is required for optimal LpL actions in vivo and that hypertriglyceridemia due to VLDLr deficiency is exacerbated by either LpL deficiency or VLDL overproduction. Fasted VLDLr knockout (VLDLr0) mice were more hypertriglyceridemic than controls (2-fold greater triglyceride levels). The hypertriglyceridemia due to VLDLr0 was even more evident when VLDLr0 mice were crossed with heterozygous LpL-deficient (LpL1) and human apolipoprotein B (apoB) transgenic mice. This was due to an increase in apoB48-containing VLDL. [(3)H]VLDL turnover studies showed that VLDL-triglyceride clearance in VLDLr0/LpL1 mice was impaired by 50% compared with LpL1 mice. VLDLr0/LpL1 mice had less LpL activity in postheparin plasma, heart, and skeletal muscle. Infection of mice with an adenovirus-expressing receptor-associated protein, an inhibitor of the VLDLr, reduced LpL activity in wild type but not VLDLr0 mice. Therefore, the VLDLr is required for normal LpL regulation in vivo, and the disruption of VLDLr results in hypertriglyceridemia associated with decreased LpL activity.

Lipoprotein lipase activation by red ginseng saponins in hyperlipidemia model animals.

The effect of ginseng saponins isolated from red ginseng (a steamed and dried root of Panax ginseng) has been studied in a cyclophosphamide (CPM)-induced hyperlipidemia model in fasted rabbits. In this model, chylomicrons and very low density lipoprotein (VLDL) accumulation was known to occur as a result of reduction in lipoprotein lipase (LPL) activity in the heart and heparin-releasable heart LPL. Oral administration of ginseng saponins at a dose of 0.01 g/kg for 4 weeks was found to reverse the increase in serum triglycerides (TG) and concomitant increase in cholesterol produced by CPM treatment, especially in chylomicrons and VLDL. In addition, ginseng saponins treatment led to a recovery in postheparin plasma LPL activity and heparin-releasable heart LPL activity, which were markedly reduced by CPM treatment. In rats given 15% glycerol/15% fructose solution, postheparin plasma LPL activity declined to two third of normal rats, whereas ginseng saponins reversed it to normal levels. In the present study we first demonstrated that ginseng saponins sustained LPL activity at a normal level or protected LPL activity from being decreased by several factors, resulting in the decrease of serum TG and cholesterol.

3-Hydroxy-3-methylglutaryl CoA reductase inhibitors reduce serum triglyceride levels through modulation of apolipoprotein C-III and lipoprotein lipase

Statins are hypolipidemic drugs which not only improve cholesterol but also triglyceride levels. Whereas their cholesterol-reducing effect involves inhibition of de novo biosynthesis of cellular cholesterol through competitive inhibition of its rate-limiting enzyme 3-hydroxy-3-methylglutaryl CoA reductase, the mechanism by which they lower triglycerides remains unknown and forms the subject of the current study. Treatment of normal rats for 4 days with simvastatin decreased serum triglycerides significantly, whereas it increased high density lipoprotein cholesterol moderately. The decrease in triglyceride concentrations after simvastatin was caused by a reduction in the amount of very low density lipoprotein particles which were of an unchanged lipid composition. Simvastatin administration increased the lipoprotein lipase mRNA and activity in adipose tissue and heart. This effect on lipoprotein lipase was accompanied by decreased mRNA as well as plasma levels of the lipoprotein lipase inhibitor apolipoprotein C-III. These results suggest that the triglyceride-lowering effect of statins involves a stimulation of lipoprotein lipase-mediated clearance of triglyceride-rich lipoproteins.

Antihyperlipidemic action of Ogi-Keishi-Gomotsu-To-Ka-Kojin against cyclophosphamide-induced hyperlipidemia in rabbits.

The effect of Ogi-Keishi-Gomotsu-To-Ka-Kojin (OKGK), a Japanese traditional herbal medicine (Kampo medicine), has been studied in a cyclophosphamide (CPM)-induced hyperlipidemia model in fasted rabbits. In this model, the accumulation of chylomicrons and very low density lipoprotein (VLDL) was known to occur as a result of a reduction in lipoprotein lipase (LPL) activity in the heart and heparin-releasable heart LPL. Oral administration of OKGK for 4 weeks was found to reverse the increase in serum triglycerides and cholesterol produced by CPM treatment especially in chyromicrons and VLDL. In addition, OKGK treatment led to a recovery in postheparin plasma LPL activity and heparin-releasable heart LPL activity which were reduced markedly by CPM treatment. We previously reported that OKGK increased LPL activity in postheparin plasma in rats. In this study, we have also found that OKGK improved hyperlipidemia in the CPM-induced hyperlipidemia model in rabbits, mainly due to an increase in heparin-releasable heart LPL activity and postheparin plasma LPL activity.

Alterations in myocardial lipid metabolism during lactation in the rat.

Metabolism of nonesterified fatty acid (palmitate, 1.1 mM) and triacylglycerol (TAG; triolein, 0.4 mM in the form of both rat chylomicrons and very low density lipoproteins) was studied in isolated perfused working hearts from fed nulliparous, lactating, and weaned rats. Hearts from virgin rats oxidized palmitate readily, but optimal cardiac mechanical performance occurred during perfusion with chylomicrons. In hearts from lactating dams, there was a significant increase in palmitate oxidation and a marked decrease in TAG oxidation from both chylomicrons and very low density lipoproteins compared with hearts from nulliparous animals. There was a concomitant decrease in lipoprotein lipase activity in hearts from lactating animals, and TAG in the absence of palmitate could not support optimal cardiac mechanical function. After litter removal, the changes in fatty acid and TAG metabolism observed in lactation returned to nulliparous values within 96 h. These results suggest that, during lactation, both exogenous and endogenous TAGs are directed away from heart and toward the lactating mammary gland; the heart, therefore, has to rely to a greater extent on nonesterified fatty acid for energy provision under these conditions.

Gene expression of lipoprotein lipase in experimental nephrosis

Nephrotic syndrome (NS) is commonly associated with marked hypertriglyceridemia, impaired triglyceride-laden lipoprotein clearance, and reduced peripheral tissue uptake of triglycerides from chylomicrons. Lipoprotein lipase (LPL) is the rate-limiting step in triglyceride-rich lipoprotein metabolism. Earlier studies have demonstrated a marked reduction of plasma post-heparin lipolytic activity and LPL protein in NS. However, the effect of NS on gene expression of LPL has not been elucidated. We studied rats with puromycin aminonucleoside-induced NS and the placebo-injected control animals. Heart, soleus muscle, and fat body LPL activity, protein mass, and mRNA were measured and plasma lipid levels were quantitated. The NS group exhibited marked proteinuria, hypoalbuminemia, and hypertriglyceridemia. This was associated with significant reductions of LPL activity and immunodetectable protein in the heart, adipose tissue, and soleus muscle in the NS group. The reduction in LPL protein mass in the tissues tested was accompanied by a parallel reduction in LPL mRNA of the heart but not of either adipose tissue or skeletal muscle, suggesting translational or posttranslational modifications. A negative correlation was found between plasma triglyceride concentration and the LPL, activities of the tissues tested in the study population. Thus this study has revealed a significant down-regulation of tissue LPL protein in experimental NS. This phenomenon can, in part, account for hypertriglyceridemia, impaired catabolism of chylomicrons, and very low-density lipoprotein by peripheral tissues and decreased postheparin lipolytic activity in NS.

Cardiac lipoprotein lipase in the spontaneously hypertensive rat.

The objectives of the present study were to determine functional (i.e., heparin-releasable) and intracellular (i.e., heparin-non-releasable) cardiac lipoprotein lipase (LPL) activity during the development of hypertension in spontaneously hypertensive (SHR) rats. Male WKY and SHR rats were killed before (7-8 weeks of age) and following (15-16 weeks of age) the development of severe hypertension in SHR rats. LPL activity in coronary perfusates was determined by retrogradely perfusing the hearts with heparin (5 U/ml). Cardiac myocytes were also isolated from the two groups of rats by collagenase digestion, and surface-bound and intracellular LPL activity measured. With the development of hypertension in SHR rats, there was a concomitant and progressive reduction in the heparin-releasable coronary endothelial LPL activity. Neither insulin action nor cell-associated enzyme activity could explain this low LPL activity in coronary blood vessels. However, acute vasodilation with nifedipine (a Ca2+ influx blocker) or CGS-21680 (A2-purinergic receptor agonist) increased the peak heparin-releasable LPL activity in hearts isolated from SHR rats. Our results indicate that hypertension per se may play a significant role in regulating cardiac LPL activity, and hence fatty acid supply to the hypertensive SHR rat heart.

Lipid metabolism in rats bearing the Yoshida AH-130 ascites hepatoma.

Rats bearing the Yoshida AH-130 ascites hepatoma showed important changes in lipid metabolism. The presence of this rapidly growing tumour induced a significant reduction in the intestinal absorption of an oral [14C]triolein load but without changes in whole body oxidation of the tracer to CO2. Both white (WAT) and brown (BAT) adipose tissue lipoprotein lipase (LPL) activities were increased at day 4 of tumour growth, changes that seem to be related with those observed in [14C]lipid accumulation; however, heart LPL activity was increased at day 7 but there was no change at day 4. In addition, there was a marked hyperlipemia in the tumour-bearing animals, whereas the blood ketone body concentrations were lower in these animals in comparison with the corresponding pair-fed group. The in vivo lipogenic rate was increased in liver of the tumour-bearing animals (day 4); conversely, it was decreased in WAT and skeletal muscle (day 4) and IBAT (day 7) of the AH-130-bearing rats. It may be suggested that the increased liver lipogenic rate associated with tumour burden is the main factor contributing to the hyperlipidaemia present in the Yoshida AH-130 bearing rats.

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

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.

Carbohydrate type and amount alter intravascular processing and catabolism of plasma lipoproteins in guinea pigs.

To test the effects of exchanging dietary complex and simple carbohydrate for fat calories on lipoprotein metabolism, guinea pigs were fed two different fat/carbohydrate ratios: 2.5:58% (w/w) or 25:29% (w/w) with either sucrose or starch as the carbohydrate source. Animals fed high-fat had higher plasma low-density lipoprotein (LDL) and hepatic cholesterol concentrations than animals fed low-fat diets (P < 0.01). The cholesteryl ester content per particle was higher, and the number of triacylglycerol (TAG) molecules was lower in very low density lipoprotein (VLDL) and LDL from animals fed high-fat diets. Intake of high-fat/sucrose resulted in higher plasma LDL concentrations than intake of high-fat/starch, and animals fed low-fat/starch had the highest plasma TAG concentrations associated with VLDL particles containing more TAG molecules, as well as a TAG-enriched LDL. The activity of plasma lecithin cholesteryl:acyl transferase (LCAT) was highest in animals fed high-fat/sucrose, and heart lipoprotein lipase (LPL) activity was higher in animals fed high-fat diets. Hepatic apoprotein B/E (apo B/E) receptor number (Bmax) was increased 21% with low-fat diets (P < 0.01). These results suggest that the hypercholesterolemia induced by high-fat and by sucrose intake are associated with a higher plasma LCAT activity which results in a cholesteryl ester-enriched VLDL which, by the action of LPL, might be more readily converted to LDL through the delipidation cascade leading to downregulation of hepatic apo B/E receptors. The hypertriglyceridemia associated with low-fat intake may result from increased production of VLDL TAG, which would explain the increased TAG content and the higher TAG/CE ratio of VLDL from animals fed the low-fat/starch diet.

Expression of lipoprotein lipase in rat muscle: regulation by feeding and hypothyroidism.

Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is found predominantly in adipose tissue and muscle. We examined the mechanism of regulation of LPL in muscles composed of different fiber types (soleus, extensor digitorum longus, and heart) in fed, fasted, and hypothyroid rats. In all muscles, the detergent-extractable (EXT) fraction represented approximately 95% of total LPL activity and mass. LPL activity was similar in the heparin-releasable (HR) fractions of heart and soleus (predominantly type I fibers), while in the EXT fraction LPL activity in soleus was 418 +/- 48 nEq/min per g, and in heart was 272 +/- 30 nEq/min per g (P < 0.05). However, LPL activity in extensor digitorum longus (EDL, predominantly type II fibers) was considerably lower (7.9 +/- 0.8 nEq/min per g in EXT, P < 0.0001 versus heart and soleus). LPL immunoreactive mass followed a pattern similar to LPL activity. LPL mRNA levels were quantitated by both Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), and were approximately equal in heart and soleus, and 5-fold lower in EDL. In response to feeding, LPL activity, mass, and mRNA levels in heart were 30% to 50% lower than in fasted rat heart, although feeding had no effect on soleus or EDL. In hypothyroid animals, muscle LPL activity was increased by 3- to 4-fold in the HR (but not EXT) fractions of heart and soleus (P < 0.05), with no change in LPL mass or mRNA. Thus, muscles with oxidative, type I fibers expressed higher levels of LPL mRNA than muscles containing glycolytic, type II fibers.(ABSTRACT TRUNCATED AT 250 WORDS)