Hepatic Lipase Activity Research Articles

The role of lipase in blood lipoprotein metabolism and accumulation of lipids in oocytes of the Siberian sturgeon Acipenser baerii during maturation

Summary The purpose of this study was to investigate the role of lipoprotein lipase (LPL) and hepatic lipase (HL) played in accumulating lipid into oocytes and serum lipid metabolism in Siberian sturgeon Acipenser baerii. We determined ovarian LPL activity, serum LPL and HL activity, and several serum lipid amounts in different ovary development stages. Our results shown that LPL activity in ovaries during vitellogenesis, serum LPL and HL activity were increased during vitellogenesis with a significant high level in stage V, and decreased fast after ovulation. Serum very low density lipoprotein (VLDL), triglycerides (TG), and phospholipids (PL) concentrations were increased since stage II to IV, and then decreased till stage VI. Serum cholesterol (TC) and low-density lipoprotein (LDL) amounts were gradually increasing during ovaries development. Moreover, we found that serum two lipases activity positively correlated with serum VLDL, TG and, TC and negatively correlated with high-density lipoprotein (HDL). The variation tendency of serum LPL, HL activity and lipids concentration, and the close correlationship between the two lipases and lipids during ovarian development suggest that LPL and HL participate in regulating blood lipid metabolism.

The effects of simvastatin treatment on plasma lipid-related biomarkers in men with dyslipidaemia

Background: Lipidomic biomarkers will facilitate the development of novel anti-atherosclerotic therapies.Objective: To evaluate the responses of circulating biomarkers to simvastatin treatment.Methods: A randomized, cross-over study in men with mixed dyslipidaemia was used to compare effects of simvastatin 40 mg/day with placebo.Results: Plasma concentrations of nine fatty acids (FA; of 33 evaluated) were reduced significantly by simvastatin. No changes in the rates of FA synthesis or in hepatic lipase or lipoprotein lipase activities were apparent. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased.Conclusion: We identified lipidomic biomarkers of simvastatin treatment effect that are consistent with statin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.Trial registration: ClinicalTrials.gov identifier: NCT00935259.

Regulation of growth performance and lipid metabolism by dietary n-3 highly unsaturated fatty acids in juvenile grass carp, Ctenopharyngodon idellus

To determine the effects of n-3 highly unsaturated fatty acids (HUFAs) in grass carp (Ctenopharyngodon idellus), a 75-day feeding experiment was conducted using five isonitrogenous and isoenergetic semi-purified diets containing 0% (control), 0.26%, 0.52%, 0.83% or 1.13% n-3 HUFAs. Weight gain, specific growth rate, feed efficiency and protein efficiency increased by increasing the dietary HUFAs content from 0% to 0.52%, and declined thereafter. Intraperitoneal fat content and the hepatopancreatic lipid levels were lowest in the 0.52% group. The tissue fatty acid level was well correlated with dietary HUFAs content. Hepatic lipoprotein lipase (LPL) activity was significantly higher in the 0.52% group, while that of malate dehydrogenase (MDH) was stable in the 0-0.52% groups, and was significantly lower in the 1.13% group. Superoxide dismutase (SOD) activity increased significantly with increasing dietary HUFAs content, consistent with the level of malondialdehyde (MDA). Hepatic mRNA expression of peroxisome proliferator-activated receptor-α (PPAR-α) was greatest in the 0.83% group and that of the LPL gene increased with increasing dietary HUFAs content up to 0.83%. These results indicate that adequate dietary HUFAs supplementation significantly promotes growth performance and lipid metabolism in freshwater fish grass carp. However, excess HUFAs fortification may exert adverse effects, which might be due to oxidative stress.

Effect of pu‐erh tea on body fat and lipid profiles in rats with diet‐induced obesity

The antiobesity and antihyperlipidaemic effects of pu-erh tea in rats with high fat diet (HFD)-induced obesity were investigated. Male Sprague-Dawley rats were randomly divided into five groups and fed varying diets for an 8-week period: control diet, HFD, and HFD supplemented with low, moderate or high doses of pu-erh tea extract (0.5 g, 2 g and 4 g/kg BW/day, respectively). Pu-erh tea significantly reduced the total body weight and the weight of various adipose pads. Pu-erh tea administration also significantly lowered plasma total cholesterol, triglyceride concentrations and low-density lipoprotein-cholesterol levels in rats with HFD-induced obesity, but did not affect high-density lipoprotein-cholesterol levels. Moreover, pu-erh tea significantly increased lipoprotein lipase, hepatic lipase and hormone-sensitive lipase activities in epididymal fat tissue in rats with HFD-induced obesity. Analysis of real-time reverse transcription-polymerase chain reaction results indicated that pu-erh tea significantly enhanced mRNA levels of hormone-sensitive lipase in rats with HFD-induced obesity. These results suggest that pu-erh tea attenuated visceral fat accumulation and improved hyperlipidemia in a rat model of HFD-induced obesity.

Interactive effects ofAPOEhaplotype, sex, and exercise on postheparin plasma lipase activities

Hepatic lipase (HL) and lipoprotein lipase (LPL) activities (HLA, LPLA) modify lipoproteins and facilitate their binding to hepatic receptors. Apolipoprotein E (APOE) physically interacts with the lipases, and the three common haplotypes of the APOE gene (ε2, ε3, and ε4) yield protein isoforms (E2, E3, and E4, respectively) that are functionally different. Lipase activities themselves differ by sex and exercise training status. The interaction of APOE genotype, exercise training, and sex effects on lipase activities has not been studied. We measured postheparin plasma lipase activities in normolipidemic men and women with the three most common APOE genotypes, which are the haplotype combinations ε2/ε3 (n = 53 ), ε3/ε3 (n = 62), and ε4/ε3 (n = 52), enrolled in 6 mo of aerobic exercise training. These haplotype combinations comprise an estimated 11.6, 62.3, and 21.3% of the population, respectively. Baseline HLA was 35% lower in women than in men (P < 0.0001). In men but not women, HLA was higher in ε2/ε3 group compared with ε4/ε3 (P = 0.01) and ε3/ε3 (P = 0.05). Neither sex nor APOE genotype affected baseline LPLA. Training decreased HLA by 5.2% (P = 0.018) with no APOE effect. The apparent increase in LPLA following exercise was significant and APOE dependent only when corrected for baseline insulin (P < 0.05). Exercise decreased LPLA by 0.8 μmol free fatty acid (FFA)·ml⁻¹·h⁻¹ (-6%) in ε3/ε3 compared with the combined increases of 6.6% in ε2/ε3 and 12% in ε4/ε3 (P = 0.018 vs. ε3/ε3). However, these differences were statistically significant only after correcting for baseline insulin. We conclude that common APOE genotypes interact with 1) sex to modulate HLA regardless of training status, with ε2/ε3 men demonstrating higher HLA than ε3/ε3 or ε4/ε3 men, and 2) aerobic training to modulate LPLA, regardless of sex, with ε3/ε3 subjects showing a significant decrease compared with an increase in ε2/ε3 and ε3/ε4 after controlling for baseline insulin.

Effects of a Purified Saponin Mixture from Alfalfa on Plasma Lipid Metabolism in Hyperlipidemic Mice

Alfalfa (Medicago sativa L.) is a genus distributed widely throughout the world and considered as the richest land source of nature products. In this study, we obtained a purified saponin mixture (PSM) through a simple, repeatable and controllable separation method from alfalfa. The compounds of the saponin mixture were identified as Azukisaponin V and Soyasaponin I, which was determined as 79.26 and 20.74% respectively by HPLC-evaporative light scattering detection (ELSD) method. The effects of PSM on plasma lipid metabolism were studied in hyperlipidemic mice induced by Triton WR-1339. Results showed that PSM could significantly inhibit the increase of total cholesterol (TC), triacylglycerol (TG) and low density lipoprotein cholesterol (LDL-C) levels, and the decrease of plasma high density lipoprotein cholesterol (HDL-C) level in plasma of hyperlipidemic mice induced by Triton WR-1339. Further study demonstrated that PSM not only enhanced the activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in liver, but also increased their mRNA levels in hyperlipidemic mice. The results above indicate that PSM from alfalfa exerts effects on plasma lipid metabolism through elevating the activity of liver lipases in hyperlipidemic mice. The obtained data would be a good contribution to the development and utilization of alfalfa in the world.

Effects of dietary lipids and Clostridium butyricum on serum lipids and lipid-related gene expression in broiler chickens

The effect of dietary lipids and Clostridium butyricum supplementation on circulating lipids and the transcription of selected genes involved in lipid metabolism were investigated in broiler chickens. One hundred and sixty-day-old broilers (Arbor Acres) were divided into four treatment groups in a 2 × 2 factorial arrangement and fed four diets with two lipid sources (soybean oil or fish oil) and two levels of C. butyricum (0 or 5 g/kg) for a period of 6 weeks. Serum concentrations of total cholesterol and low-density lipoprotein cholesterol were lower (P < 0.05) in broilers fed diets containing fish oil than in those fed diets containing soybean oil. Fish oil significantly reduced (P < 0.05) hepatic fatty acid synthase and lipoprotein lipase (LPL) activities in abdominal fat. In contrast, fish oil significantly increased (P < 0.05) breast muscle LPL activity and hepatic peroxisome proliferator-activated receptor-α and LPL gene expression. The addition of C. butyricum significantly increased (P < 0.05) LPL activity in abdominal fat and liver-type fatty acid-binding protein gene expression in jejunal mucosa. The results of this study indicated that the reduced abdominal fat in broilers fed fish oil as observed may be due to augmented hepatic fatty acid catabolism and lower hepatic fat synthesis. The increased intramuscular fat content in breast muscle of broilers fed C. butyricum as described may be the result of enhanced fatty acid uptake.

Does non-alcoholic fatty liver impair alterations of plasma lipoproteins and associated factors in metabolic syndrome?

Background Hepatic steatosis (HS) is closely associated to metabolic syndrome (MS). Both, VLDL-triglyceride oversecretion and intrahepatic deposits, can take place. We evaluated VLDL characteristics, CETP, hepatic lipase (HL), IDL and small dense LDL (sdLDL), in patients with HS associated to MS. Methods We studied 3 groups matched by age and sex: 25 MS patients with HS (diagnosed by ultrasonography), 25 MS patients without HS and 25 healthy controls. Main measurements were: lipid profile, free fatty acids, VLDL composition, VLDL size by HPLC, CETP and HL activities, IDL-cholesterol and sdLDL-cholesterol. Results Patients with HS presented higher triglyceride levels, HOMA-IR and free fatty acids, VLDL mass and VLDL-apoB (p < 0.05). No differences in VLDL composition were observed. MS groups presented higher proportion of large VLDL than controls (p < 0.05). HS group showed higher CETP than controls (p = 0.01) and almost higher than MS without HS (p = 0.06). CETP correlated with VLDL-cholesterol content, r = 0.48, p < 0.005. The increase in sdLDL-cholesterol correlated with CETP (r = 0.47) and HL (r = 0.56), independent of insulin resistance (p < 0.003). Conclusion Despite intrahepatic fat, patients with HS secreted higher number of VLDL particles. CETP would have a remodeling action on VLDL in circulation, enriching it in cholesterol and also favoring, together with HL, the formation of sdLDL.

Effect of dietary conjugated linoleic acid (CLA) on growth performance, body composition and hepatic intermediary metabolism in juvenile yellow catfish Pelteobagrus fulvidraco

The present study was conducted to determine the effect of dietary conjugated linoleic acid (CLA) on growth performance, body composition and hepatic intermediary metabolism in juvenile yellow catfish Pelteobagrus fulvidraco (initial body weight: 1.87 ± 0.04 g, mean ± SD). The five isonitrogenous (35% crude protein) experimental diets were formulated to contain graded CLA levels of 0 (control), 0.5, 1, 1.5 and 2%, respectively. Three replicated groups of fish were fed to satiation, twice a day, over a period of 8 weeks with CLA oil, containing mainly the bioactive cis-9, trans-11 and trans-10, and cis-12 isomers. The increase of dietary CLA levels reduced growth performance, feed conversion rate (FCR), condition factor, hepatosomatic index and viscerosomatic index of yellow catfish. Increasing dietary CLA levels significantly reduced lipid contents in the whole body and liver. The dietary inclusion of CLA modified total percentages of the main groups of fatty acids. Increasing saturated fatty acid (SFA) content and reduced mono-unsaturated fatty acid (MUFA) contents in the whole body were observed with increasing dietary CLA inclusion. A gradual reduction of 16:1 and 18:1 fatty acids was depicted in the whole body with increasing CLA levels. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) profiles showed no significant differences among the treatments. Total polyunsaturated fatty acids (PUFA) tended to increase with increasing dietary CLA levels. Dietary CLA supplementation resulted in a significant increase of the trans-10, cis-12 and cis-9, and trans-11 CLA isomers in the whole body, and also significantly influenced several hepatic enzymatic activities, such as succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), malic dehydrogenase (MDH), lipoprotein lipase (LPL) and hepatic lipase (HL) activities. These indicate that despite promoting the CLA and PUFA deposition in the whole body, dietary CLA supplementation should be carefully evaluated in intensive yellow catfish farming as it reduces growth performance and feed utilization.

Postprandial Lipid-Related Metabolites Are Altered in Dogs Fed Dietary Diacylglycerol and Low Glycemic Index Starch during Weight Loss1–3

In this study, we investigated a combination of a low glycemic index starch (LGIS) and diacylglycerol (DAG) on lipid, lipoprotein (LP) metabolism, and weight management. Obese, intact female adult Beagle dogs were assigned to 1 of 4 starch/oil combination diets [LGIS/DAG (LD); LGIS/triacylglycerol (TAG); high glycemic index starch (HGIS)/DAG; and HGIS/TAG (HT)] and fed for 9 wk (n = 6/group) using an incomplete 4 × 4 Latin square design. Each dog was fed 1 of 2 opposite starch/oil combination diets (e.g. LD and HT). At wk 1 and 8, postprandial blood was collected for plasma triacylglycerol (TG), β-hydroxybutyrate (BHB), total cholesterol (TC), and LP analyses. During the same week, dogs were overnight feed-deprived and post-heparin blood was collected for LP lipase and hepatic lipase activity determinations. At wk 1, 4, and 8, blood was drawn from overnight feed-deprived dogs for plasma TG, BHB, TC, LP, leptin, and adiponectin measurements. Feces were collected at wk 3 for digestibility calculations. The LGIS diets resulted in lower carbohydrate, protein, total tract dry matter digestibilities, and metabolizable energy compared with the HGIS diet groups (P < 0.05). Thus, the LGIS groups lost more body weight (P = 0.001), which was positively correlated with plasma leptin concentrations (r2 = 0.427; P < 0.001). Moreover, the LGIS diet lowered TC concentrations in combination with DAG. The DAG diet groups decreased postprandial TG and increased BHB concentrations (P < 0.05). Starch/oil types did not alter lipase activities or adiponectin concentrations. In conclusion, the LGIS diet demonstrated potential as a weight management tool in dogs by decreasing postprandial TG and increasing BHB in combination with DAG.

Effects of different diets on weight gain,hepatic lipase and antioxidant enzyme of juvenile silver pomfret(&lt;I&gt;Pampus argenteus&lt;/I&gt;)

A 9-week feeding experiment was carried out on juvenile silver pomfret Pampus argenteus[initial weight,(4.80±0.11) g]to evaluate the effects of feed composition on weight gain,feed conversion ratio(FCR),hepatic lipase and antioxidant enzyme activities using nutriology and biochemistry.Four diets were formulated and named diet 1(fresh fish meat),diet 2(fresh fish meat mixed with formulated feed),diet 3(fresh fish meat mixed with formulated feed and solen meat) and diet 4(fresh fish meat mixed with formulated feed,solen meat and copepods).Each diet was assigned to triplicate groups.The results showed that the weight gain of silver pomfret could be affected significantly by the feed composition.The weight gain of diet 1 was the lowest among the four diets,and was significantly lower than those of other three diets.The weight gain of diet 4 was the highest,and was significantly higher than those of diet 2 and diet 3(P0.05).The FCR of diet 1 was the highest among the four diets,and was significantly higher than those of other three diets.There was no significant difference in FCR among diet 2,diet 3 and diet 4(P0.05).Hepatic lipase and total lipase activities of diet 1 were significantly lower than those of other diets(P0.05),but no significant difference was found in hepatic lipase,lipoprotein lipase and total lipase activities among diet 2,diet 3 and diet 4(P0.05).There was no significant difference in superoxide dismutase(SOD) and glutathione peroxidase(GSH-PX) activities among all diets(P0.05).However,the lowest SOD and GSH-PX activities were both in diet 1 and highest were in diet 4.The catalase(CAT) activity of diet 4 was significantly higher than those of diet 1,2 and 3(P0.05),but no significant difference was found among diet 1,2 and 3(P0.05).In conclusion,the only use of fish meat as a feed is not beneficial to the growth of silver pomfret.Copepods could be also used in the diet to improve the growth and antioxidant ability of silver pomfret.

Update on CETP inhibition

Cholesteryl ester transfer protein (CETP) plays an important role in reverse cholesterol transport and the maintenance of cholesterol homeostasis. The consequences of CETP activity are influenced by triglyceride (TG) levels. When TG levels are increased, CETP promotes transfer of cholesteryl esters to VLDL and the generation of atherogenic dyslipidemia. Combined activities of CETP and hepatic lipase in the presence of TG-rich lipoproteins generate small, dense HDL and LDL particles. Inhibition of CETP may reduce the risk of atherosclerosis in patients with dyslipidemia. Decreasing CETP activity has consistently inhibited atherosclerosis in animal models. Three small-molecule CETP inhibitors, dalcetrapib, torcetrapib, and anacetrapib, have been or are being tested in phase 3 clinical studies. All three demonstrated potentially beneficial effects on the lipid profile in patients with dyslipidemia. Imaging studies with torcetrapib failed to show an effect on atherosclerosis in humans, probably because of the off-target effect on the RAAS. Preclinical evidence suggests that dalcetrapib seems to lack the off-target adverse effects on the RAAS that potentially caused the clinical development of torcetrapib to be halted. The lack of adverse effects on the RAAS remains to be confirmed in phase 3 studies with dalcetrapib. CETP inhibition as a therapeutic strategy remains a valid option to be tested with a CETP inhibitor that does not share torcetrapib's off-target effects.

Effects of Theabrownin from Pu‐erh Tea on the Metabolism of Serum Lipids in Rats: Mechanism of Action

Theabrownin (TB), one of the main bioactive components in pu-erh tea, has a significant blood lipid-lowering effect in hyperlipidemic rats. Therefore, it was hypothesized that TB would regulate the activity of key enzymes involved in lipid metabolism and accelerate the catabolism of exogenous cholesterol in rats fed a high fat diet. A total of 90 Sprague-Dawley rats were randomly divided into a normal control group (Group I), a high fat diet group (Group II), and high-fat diet plus TB group (Group III). A total of 10 rats were selected from each group and killed at 15, 30, or 45 d after starting the study for analysis. After feeding 45 d, the contents of TC, TG, and LDL-C levels in Group II were increased by 54.9%, 93.1%, and 134.3% compared with those in Group III, respectively, and the content of HDL-C in Group II was decreased by 55.7%. These effects were inhibited in the rats in Group III, which exhibited no significant differences in these levels compared with Group I, indicating that TB can prevent hyperlipidemia in rats fed a high fat diet. TB enhanced the activity of hepatic lipase and hormone-sensitive triglyceride lipase (HSL) and increased the HSL mRNA expression in liver tissue and epididymis tissue. The HL activity in serum of Group III was increased by 147.6% compared with that in Group II. The content of cholesterol and bile acid in the feces of rats was increased by 21.11- and 4.08-fold by TB. It suggested that TB could promote the transformation and excretion of dietary cholesterol of rats in vivo.

Association of angiopoietin-like protein 3 with hepatic triglyceride lipase and lipoprotein lipase activities in human plasma

The relationship between plasma angiopoietin-like protein 3 (ANGPTL3), and lipoprotein lipase (LPL) activity and hepatic triglyceride lipase (HTGL) activity has not been investigated in the metabolism of remnant lipoproteins (RLPs) and high-density lipoprotein (HDL) in human plasma. ANGPTL3, LPL activity, HTGL activity, RLP-C and RLP-TG and small, dense LDL-cholesterol (sd LDL-C) were measured in 20 overweight and obese subjects in the fasting and postprandial states. Plasma TG, RLP-C, RLP-TG and sd LDL-C were inversely correlated with LPL activity both in the fasting and postprandial states, but not correlated with HTGL activity and ANGPTL3. However, plasma HDL-C was positively correlated with LPL activity both in the fasting and postprandial states, while inversely correlated with HTGL activity. ANGPTL3 was inversely correlated with HTGL activity both in the fasting and postprandial states, but not correlated with LPL activity. HTGL plays a major role in HDL metabolism, but not RLP metabolism. These findings suggest that ANGPTL3 is strongly associated with the inhibition of HTGL activity and regulates HDL metabolism, but not associated with the inhibition of LPL activity for the metabolism of RLPs in human plasma.

MS407 REDUCED MYOCARDIAL GLUCOSE UTILIZATION AFTER FASTING AND HEPARIN INJECTION IN RATS

Type III hyperlipoproteinemia (HLP), a disorder associated with a high incidence of premature cardiovascular diseases, is characterized by the accumulation of remnant lipoproteins in the plasma. The primary genetic defect in patients with type III HLP is the presence of apolipoprotein E2 (apoE2), an isoform of apoE, and accumulation of remnant lipoproteins in the plasma has been thought to be attributable to the presence of apoE2, which bind poorly to low density lipoprotein receptors, resulting in defective remnant lipoprotein clearance. On the other hand, the activity of hepatic lipase (HL), the enzyme that plays a pivotal role in the removal of remnant lipoproteins, in type III HLP has not been investigated.We examined post-heparin plasma lipoprotein lipase (LPL) and HL activities in 7 patients with type III HLP. The activities of HL and LPL in post-heparin plasma were measured separately by an immunochemical method using antiserum specifically directed against HL.The post-heparin plasma HL activity was significantly reduced, while the LPL activity was normal.Reduced HL activity may account, at least in part, for the accumulation of remnant lipoproteins in the plasma, a characteristic feature of type III HLP.

Exchanging Carbohydrate or Protein for Fat Improves Lipid-Related Cardiovascular Risk Profile in Overweight Men and Women When Consumed Ad Libitum

BackgroundThe impact of low-fat diets on the plasma lipoprotein profile is incompletely understood.MethodsWe conducted two 16-week dietary studies to compare the effects of a moderate-fat (mod-FAT) baseline diet with isocaloric...

Different effects of pioglitazone and rosiglitazone on lipid metabolism in mouse cultured liver explants

Pioglitazone (PIO) and rosiglitazone (ROSI) are widely used as oral antidiabetic agents for treatment of type 2 diabetes. Although these medications exert similar effects on blood glucose, recent clinical studies indicated that PIO has a more pronounced beneficial effect on lipid parameters than ROSI. In order to get further insight into the lipid effects of both drugs, we tested whether PIO, compared to ROSI, could exert direct effects on lipid liver metabolism in relation with plasma lipids. We performed in vitro studies using mice liver slices incubated 21 h either with ROSI (1 micromol/L) or PIO (7.5 micromol/L). We showed that both glitazones slightly reduced HMG-CoA reductase mRNA levels at the same degree but only PIO reduced intracellular cholesterol content, suggesting an alteration of cholesterol uptake rather than an inhibition of cholesterol biosynthesis. This concept was supported by the reduction of scavenger receptor class B type I expression, hepatic lipase activity and high-density lipoprotein cholesterol uptake in PIO-treated liver explants. Conversely, hepatic lipase mRNA levels were increased 3.5-fold. ROSI, but not PIO, induced acetyl-CoA carboxylase and fatty acid synthase gene expression and increased apoB secretion suggesting a stimulation of lipogenesis. Concurrently, peroxisome proliferator-activated receptor-gamma mRNA levels were induced by ROSI and not significantly changed by PIO. Besides, PIO appeared to be a more potent activator of AMP-Activated Protein Kinase than ROSI. PIO and ROSI exert specific direct effects on liver and extrapolating these data to humans could explain the significant improvements in plasma lipids observed in diabetic patients treated with PIO.

Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size

The structural features responsible for the activities of hepatic lipase (HL) can be clarified by in vivo comparisons of naturally occurring variants. The coding sequence of HL from C57BL/6J (B6) and SPRET/EiJ (SPRET) mice differs by four amino acids (S106N, A156V, L416V, S480T); however, these changes are not predicted to influence HL function. To test for allelic effects, we generated SPRET-HL transgenics with physiological levels of HL mRNA and HL activity that was parallel in female transgenics and about 70% higher in male transgenics, toward tri-[3H]oleate, compared with B6 controls. We found no correlation between activity levels and plasma lipids. However, significant allelic effects on plasma lipids were observed. Compared with B6-HL, SPRET-HL mediated reductions in total cholesterol (TC) and VLDL-, LDL- and HDL-cholesterol and HDL-triglyceride (TG) in fed males, and SPRET-HL decreased total TG and VLDL- and HDL-TG levels in fasted males. Fasted female transgenics had reduced TC compared with controls. We also found allele and sex effects on lipoprotein particle size. Male transgenic mice had increased VLDL and decreased LDL size, and female transgenic mice had decreased HDL size compared with control animals. These findings demonstrate highly divergent effects of naturally occurring HL coding sequence variants on lipid and lipoprotein metabolism.

Effects of farnesoid X receptor on the expression of the fatty acid synthetase and hepatic lipase

The farnesoid X receptor (FXR) is a nuclear receptor that regulates gene expression in response to bile acids (BAs). FXR plays an important role in the homeostasis of bile acid, cholesterol, lipoprotein and triglyceride. In this report, we identified fatty acid synthase (FAS) and hepatic lipase (HL) genes as novel target genes of FXR. Human hepatoma HepG2 cells were treated with chenodeoxycholic acid, the natural FXR ligand, and the messenger RNA and protein levels of FAS and HL were determined by RT-PCR and Western blot analysis, respectively. Chenodeoxycholic acid (CDCA) down-regulated the expression of FAS and HL genes in a dose and time-dependent manner in human hepatoma HepG2 cells. In addition, treatment of mice with CDCA significantly decreased the expression of FAS and HL in mouse liver and the activity of HL. These results demonstrated that FAS and HL might be FXR-regulated genes in liver cells. In view of the role of FAS and HL in lipogenesis and plasma lipoprotein metabolism, our results further support the central role of FXR in the homeostasis of fatty acid and lipid.

The eSS rat, a nonobese model of disordered glucose and lipid metabolism and fatty liver.

BackgroundeSS is a rat model of type 2 diabetes characterized by fasting hyperglycemia, glucose intolerance, hyperinsulinemia and early hypertriglyceridemia. Diabetic symptoms worsen during the second year of life as insulin release decreases. In 12-month-old males a diffuse hepatic steatosis was detected. We report the disturbances of lipid metabolism of the model with regard to the diabetic syndrome.MethodsThe study was conducted in eight 12-month-old eSS male rats and seven age/weight matched eumetabolic Wistar rats fed with a complete commercial diet al libitum. Fasting plasmatic glucose, insulin, triglycerides, total cholesterol, low-density and high-density lipoprotein, and nonesterified fatty acids levels were measured. Very low density and intermediate-density lipoproteins were analyzed and hepatic lipase activity was determined.ResultseSS rats developed hyperglycemia and hyperinsulinemia, indicating insulin resistance. Compared with controls, diabetic rats exhibited high plasmatic levels of NEFA, triglycerides (TG), total cholesterol (Chol) and LDL-Chol while high-density lipoprotein (HDL) cholesterol values were reduced. eSS rats also displayed TG-rich VLDL and IDL particles without changes in hepatic lipase activity.ConclusionThe nonobese eSS rats develop a syndrome characterized by glucose and lipid disorders and hepatic steatosis that may provide new opportunities for studying the pathogenesis of human type 2 diabetes.