Very Low Density Lipoprotein Triglyceride Research Articles

Systemic Delivery of Estradiol, but not Testosterone or Progesterone, Alters Very Low Density Lipoprotein-Triglyceride Kinetics in Postmenopausal Women

Sexual dimorphism in plasma triglyceride (TG) metabolism is well established but it is unclear to what extent it is driven by differences in the sex hormone milieu. RESULTS from previous studies evaluating the effects of sex steroids on plasma TG homeostasis are inconclusive because they relied on orally administered synthetic hormone preparations or evaluated only plasma lipid concentrations but not kinetics. The purpose of this study was to evaluate the effects of systemically delivered 17β-estradiol, progesterone, and T on very low density lipoprotein-triglyceride (VLDL-TG) concentration and kinetics in postmenopausal women. VLDL-TG concentration and kinetics were evaluated by using stable isotope-labeled tracer techniques in four groups of postmenopausal women (n = 27 total) who were studied before and after treatment with either 17β-estradiol (0.1 mg/d via continuous delivery skin patch), progesterone (100 mg/d via vaginal insert) and T (12.5 mg/d via skin gel), or no intervention (control group). VLDL-TG concentration and kinetics were unchanged in the control group and not altered by T and progesterone administration. Estradiol treatment, in contrast, reduced VLDL-TG concentration by approximately 30% due to accelerated VLDL-TG plasma clearance (25.1 ± 2.5 vs. 17.4 ± 2.7 mL/min; P < .01). Estradiol, but not progesterone or T, is a major regulator of VLDL-TG metabolism.

The SORT1 risk allele is associated with exaggerated postprandial lipaemia in young adults (383.5)

Elevations in low‐density lipoproteins (LDL), very‐low density lipoproteins (VLDL) and triglycerides (TG) in the postprandial state have a strong genetic component and recognized atherogenic potential. We sought to determine if there is a difference in postprandial lipaemia following an oral fat tolerance test when stratified by genotype at the SORT1 1p13 locus, the strongest LDL‐cholesterol associated locus identified to date. Thirty, healthy young adults (age=23.57) received a high fat, mixed meal (91 g, 55% kcal from fat). Blood samples drawn at fasting, 2, 4, 8 and 24 hrs postprandial, underwent comprehensive lipoprotein analyses via nuclear magnetic resonance profiling. At fasting, VLDL particles differed based upon SORT1 genotype (TT: 48.81±5.07 nmol/L versus TC/CC: 30.05±2.99 nmol/L, p=0.004). Major, risk allele homozygotes (TT) had significantly elevated area‐under‐the‐curve and mean concentration for VLDL particles, TG and VLDL‐TG (p&lt;0.05). These results indicate increased fasting and postprandial exposure to atherogenic particles in TT homozygotes. This highlights SORT1 as a valuable target for identifying individuals for early, personalized interventions to prevent atherosclerosis.

Relation of Periodontitis and Metabolic Syndrome With Gestational Glucose Metabolism Disorder

Gestational diabetes mellitus (GDM) and metabolic syndrome have been related to periodontitis. This study's objective is to establish the relationship between them in pregnant women affected by gestational glucose metabolism disorder. In 188 pregnant women with positive O'Sullivan test (POT) results, an oral glucose tolerance test (OGTT) was performed to diagnose GDM. The mother's periodontal parameters, age, prepregnancy weight and height and body mass index (BMI), blood pressure, gestational age, and birth weight were recorded at 24 to 28 weeks of pregnancy, as well as levels of glucose, C-reactive protein, triglycerides, glycated hemoglobin (HbA1c), and total, low-density lipoprotein, high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL) cholesterol levels. Prepregnancy weight, prepregnancy BMI, systolic and diastolic blood pressure, VLDL cholesterol, and glucose parameters were higher in GDM compared with POT (P <0.05). VLDL cholesterol, triglycerides, and 2-hour OGTT were higher in patients with periodontitis than in patients without periodontitis (P <0.05). HbA1c, triglycerides, and 1- and 2-hour OGTT were positively related with probing depth and clinical attachment level; blood glucose was related only to bleeding on probing (P <0.05). HbA1c, basal OGTT, and 1- and 2-hour OGTT were positively related to prepregnancy BMI and blood pressure; HDL cholesterol was negatively related to prepregnancy BMI; C-reactive protein was positively related to prepregnancy BMI and diastolic blood pressure (P <0.05). These data support the relationships among periodontal disease and some biochemical parameters such as lipid and glucose data in pregnancy, and also among metabolic syndrome and biochemical parameters.

Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg) mice, which predominantly excrete cholesterol via TICE, and wild type (WT) littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG) and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism.

Icosapent ethyl: A novel drug for hypertriglyceridemia

Icosapent ethyl is a lipid regulating drug which was recently given a green signal from FDA. It is used as an adjunct drug along with diet control to lower triglycerides in those patients who present with very high levels. It lowers the production and/or secretion of very low-density lipoprotein triglycerides (VLDL-TG) in liver and augments triglyceride clearance from VLDL particles.

Saturated fatty acids activate ERK signaling to downregulate hepatic sortilin 1 in obese and diabetic mice

Hepatic VLDL overproduction is a characteristic feature of diabetes and an important contributor to diabetic dyslipidemia. Hepatic sortilin 1 (Sort1), a cellular trafficking receptor, is a novel regulator of plasma lipid metabolism and reduces plasma cholesterol and triglycerides by inhibiting hepatic apolipoprotein B production. Elevated circulating free fatty acids play key roles in hepatic VLDL overproduction and the development of dyslipidemia. This study investigated the regulation of hepatic Sort1 in obesity and diabetes and the potential implications in diabetic dyslipidemia. Results showed that hepatic Sort1 protein was markedly decreased in mouse models of type I and type II diabetes and in human individuals with obesity and liver steatosis, whereas increasing hepatic Sort1 expression reduced plasma cholesterol and triglycerides in mice. Mechanistic studies showed that the saturated fatty acid palmitate activated extracellular signal-regulated kinase (ERK) and inhibited Sort1 protein by mechanisms involving Sort1 protein ubiquitination and degradation. Consistently, hepatic ERK signaling was activated in diabetic mice, whereas blocking ERK signaling by an ERK inhibitor increased hepatic Sort1 protein in mice. These results suggest that increased saturated fatty acids downregulate liver Sort1 protein, which may contribute to the development of dyslipidemia in obesity and diabetes.

Insulin-like growth factor-1 and lipoprotein profile in cord blood of preterm small for gestational age infants

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at <37-week gestational age, including 10 small for gestational age (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P < 0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P < 0.001), and negatively with log TG (r = -0.484, P = 0.002) and log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level.

Systemic Free Fatty Acid Disposal Into Very Low-Density Lipoprotein Triglycerides

We measured the incorporation of systemic free fatty acids (FFA) into circulating very low-density lipoprotein triglycerides (VLDL-TGs) under postabsorptive, postprandial, and walking conditions in humans. Fifty-five men and 85 premenopausal women with BMI 18–24 (lean) and 27–36 kg/m2 (overweight/obese) received an intravenous bolus injection of [1,1,2,3,3-2H5]glycerol (to measure VLDL-TG kinetics) and either [1-14C]palmitate or [9,10-3H]palmitate to determine the proportion of systemic FFA that is converted to VLDL-TG. Experiments started at 0630 h after a 12-h overnight fast. In the postabsorptive protocol, participants rested and remained fasted until 1330 h. In the postprandial protocol, volunteers ingested frequent portions of a fat-free smoothie. In the walking protocol, participants walked on a treadmill for 5.5 h at ∼3× resting energy expenditure. Approximately 7% of circulating FFA was converted into VLDL-TG. VLDL-TG secretion rates (SRs) were not statistically different among protocols. Visceral fat mass was the only independent predictor of VLDL-TG secretion, explaining 33–57% of the variance. The small proportion of systemic FFA that is converted to VLDL-TG can confound the expected relationship between plasma FFA concentration and VLDL-TG SRs. Regulation of VLDL-TG secretion is complex in that, despite a broad spectrum of physiological FFA concentrations, VLDL-TG SRs did not vary based on different acute substrate availability.

Effect of an isoenergetic traditional Mediterranean diet on apolipoprotein A-I kinetic in men with metabolic syndrome

BackgroundThe impact of the Mediterranean diet (MedDiet) on high-density lipoprotein (HDL) kinetics has not been studied to date. The objective of this study was therefore to investigate the effect of the MedDiet in the absence of changes in body weight on apolipoprotein (apo) A-I kinetic in men with metabolic syndrome (MetS).MethodsTwenty-six men with MetS (NCEP-ATP III) were recruited from the general community. In this fixed sequence study, participants’ diet was first standardized to a control diet reflecting current averages in macronutrient intake in North American men, with all foods and beverages provided under isoenergetic conditions for 5 weeks. Participants were then fed an isoenergetic MedDiet over a subsequent period of 5 weeks to maintain their weight constant. During the last week of each diet, participants received a single bolus dose of [5,5,5-2H3] L-leucine and fasting blood samples were collected at predetermined time points. ApoA-I kinetic was determined by multicompartmental modeling using isotopic enrichment data over time. Data were analyses using MIXED models.ResultsThe response of HDL-cholesterol (C) to MedDiet was heterogeneous, such that there was no mean change compared with the control diet. Plasma apoA-I concentration (−3.9%) and pool size (−5.3%, both P < 0.05) were significantly lower after MedDiet and apoA-I production rate tended to be reduced (−5.7%, P = 0.07) with no change in apoA-I fractional catabolic rate (FCR, -1.6%, P = 0.64). Participants among whom HDL-C concentrations were increased with MedDiet (responders: mean ∆HDL-C: +9.9 ± 3.2%, N = 11) showed significantly greater reductions in apoA-I FCR and in apoB and very-low-density lipoprotein-triglycerides (VLDL-TG) concentrations (all P < 0.04) than those among whom HDL-C levels were reduced after the MedDiet (non-responders: mean ∆HDL-C: -12.0 ± 3.9%, N = 8). Correlation analysis revealed that only variations in apoA-I FCR (r = -0.48, P = 0.01) and in plasma VLDL-TG (r = −0.45, P = 0.03) concentrations were correlated with the individual HDL-C response to the MedDiet.ConclusionsData from this controlled feeding study suggest that the heterogeneous response of HDL-C to MedDiet, in the absence of important weight loss, is primarily related to individual variations in apoA-I FCR and in plasma VLDL-TG concentrations.Trial registrationClinicalTrial.gov registration number: NCT00988650

Effect of Acute Negative and Positive Energy Balance on Basal Very-Low Density Lipoprotein Triglyceride Metabolism in Women

BackgroundAcute reduction in dietary energy intake reduces very low-density lipoprotein triglyceride (VLDL-TG) concentration. Although chronic dietary energy surplus and obesity are associated with hypertriglyceridemia, the effect of acute overfeeding on VLDL-TG metabolism is not known.ObjectiveThe aim of the present study was to investigate the effects of acute negative and positive energy balance on VLDL-TG metabolism in healthy women.DesignTen healthy women (age: 22.0±2.9 years, BMI: 21.2±1.3 kg/m2) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) isocaloric feeding (control) ii) hypocaloric feeding with a dietary energy restriction of 2.89±0.42 MJ and iii) hypercaloric feeding with a dietary energy surplus of 2.91±0.32 MJ. The three diets had the same macronutrient composition.ResultsFasting plasma VLDL-TG concentrations decreased by ∼26% after hypocaloric feeding relative to the control trial (P = 0.037), owing to decreased hepatic VLDL-TG secretion rate (by 21%, P = 0.023) and increased VLDL-TG plasma clearance rate (by ∼12%, P = 0.016). Hypercaloric feeding increased plasma glucose concentration (P = 0.042) but had no effect on VLDL-TG concentration and kinetics compared to the control trial.ConclusionAcute dietary energy deficit (∼3MJ) leads to hypotriglyceridemia via a combination of decreased hepatic VLDL-TG secretion and increased VLDL-TG clearance. On the other hand, acute dietary energy surplus (∼3MJ) does not affect basal VLDL-TG metabolism but disrupts glucose homeostasis in healthy women.

Omega-3 fatty acid ethyl ester supplementation decreases very-low-density lipoprotein triacylglycerol secretion in obese men

Dysregulated VLDL-TAG (very-low-density lipoprotein triacylglycerol) metabolism in obesity may account for hypertriacylglycerolaemia and increased cardiovascular disease. ω-3 FAEEs (omega-3 fatty acid ethyl esters) decrease plasma TAG and VLDL concentrations, but the mechanisms are not fully understood. In the present study, we carried out a 6-week randomized, placebo-controlled study to examine the effect of high-dose ω-3 FAEE supplementation (3.2g/day) on the metabolism of VLDL-TAG in obese men using intravenous administration of d5-glycerol. We also explored the relationship of VLDL-TAG kinetics with the metabolism of VLDL-apo (apolipoprotein) B-100 and HDL (high-density lipoprotein)-apoA-I. VLDL-TAG isotopic enrichment was measured using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Compared with placebo, ω-3 FAEE supplementation significantly lowered plasma concentrations of total (-14%, P<0.05) and VLDL-TAG (-32%, P<0.05), as well as hepatic secretion of VLDL-TAG (-32%, P<0.03). The FCR (fractional catabolic rate) of VLDL-TAG was not altered by ω-3 FAEEs. There was a significant association between the change in secretion rates of VLDL-TAG and VLDL-apoB-100 (r=0.706, P<0.05). However, the change in VLDL-TAG secretion rate was not associated with change in HDL-apoA-I FCR (r=0.139, P>0.05). Our results suggest that the TAG-lowering effect of ω-3 FAEEs is associated with the decreased VLDL-TAG secretion rate and hence lower plasma VLDL-TAG concentration in obesity. The changes in VLDL-TAG and apoB-100 kinetics are closely coupled.

分娩前後の乳牛のリポタンパク質中のコレステロール値とトリグリセリド値のプロファイル

Lipoproteins are macromolecule complexes of protein, phospholipids, cholesterol, cholesterol esters, and triglycerides, and the lipoproteins transport cholesterol and triglycerides throughout the animal body. The objective of the present study was to investigate a profile of cholesterol and triglyceride concentrations in four lipoproteins during the peripartum period in Holstein dairy cows. Sixty nine blood samples for lipoprotein analysis were taken from 41 periparturient cows on 16 dairy farms. The analysis determined cholesterol and triglyceride concentrations in four lipoprotein fractions which included chylomicron (CM), very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL). Analysis of covariance compared cholesterol and triglyceride concentrations in four lipoprotein fractions between pre- and post-partum periods in cows. Correlation analysis was performed between cholesterol and triglyceride concentrations in the four lipoproteins. Means (±SEM) of total concentrations of cholesterol and triglyceride in pre-partum cows were 83.61 (±3.9) and 14.1 (±0.69) and mg/dl, respectively. After calving, the total concentrations of cholesterol and triglyceride decreased to 70.31 (±4.07) and 5.53 (±0.57) mg/dl, respectively. The highest HDL cholesterol concentration and the highest VLDL triglyceride concentration were found among the four lipoprotein fractions. Cholesterol concentrations in all the four fractions decreased from pre-partum to post-partum periods (P<0.05), whereas triglyceride concentrations in the two fractions of VLDL and CM decreased (P<0.05). Especially, VLDL cholesterol and VLDL triglyceride concentrations decreased by 70% or higher. In both pre-partum periods and post-partum periods, cholesterol concentrations were correlated between VLDL, LDL and HDL (P<0.05), but no such correlations were found for triglyceride concentrations. In conclusion, cholesterol and triglyceride concentrations in four fractions are differently related with the calving in dairy cows.

The strange and critical intersection of hepatitis C and lipoprotein metabolism: “C-zing” the oil

Since its discovery in 1989, a substantial amount of research has emerged regarding the close association of hepatitis C virus (HCV) replication and hepatic lipoprotein metabolism. Even before the identification of the HCV virus, a link to fat metabolism was suspected based on clinical observations regarding steatosis as a common feature of what used to be known as “non-A, non-B hepatitis.”1 This relationship was later extended in studies that revealed that HCV-infected patients with steatosis often lack common risk factors for fatty liver, such as obesity.2 These early observations, along with subsequent studies that identified circulating viral particles in low-density, more-buoyant plasma fractions (partitioned with plasma centrifugation in sucrose or iodixanol gradients), fueled a now extensive and growing body of literature on this key aspect of HCV replication.3 Investigations performed over the past 23 years have defined replicative pathways of HCV involving mechanisms and biochemical pathways right out of the “play book” of fatty liver disease (FLD).

Liver specific inactivation of carboxylesterase 3/triacylglycerol hydrolase decreases blood lipids without causing severe steatosis in mice

Carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) participates in hepatic very low-density lipoprotein (VLDL) assembly and in adipose tissue basal lipolysis. Global ablation of Ces3/Tgh expression decreases serum triacylglycerol (TG) and nonesterified fatty acid levels and improves insulin sensitivity. To understand the tissue-specific role of Ces3/TGH in lipid and glucose homeostasis, we generated mice with a liver-specific deletion of Ces3/Tgh expression (L-TGH knockout [KO]). Elimination of hepatic Ces3/Tgh expression dramatically decreased plasma VLDL TG and VLDL cholesterol concentrations but only moderately increased liver TG levels in mice fed a standard chow diet. Significantly reduced plasma TG and cholesterol without hepatic steatosis were also observed in L-TGH KO mice challenged with a high-fat, high-cholesterol diet. L-TGH KO mice presented with increased plasma ketone bodies and hepatic fatty acid oxidation. Intrahepatic TG in L-TGH KO mice was stored in significantly smaller lipid droplets. Augmented hepatic TG levels in chow-fed L-TGH KO mice did not affect glucose tolerance or glucose production from hepatocytes, but impaired insulin tolerance was observed in female mice. Our data suggest that ablation of hepatic Ces3/Tgh expression decreases plasma lipid levels without causing severe hepatic steatosis.

Effect of cholesterol on lipogenesis and VLDL–TG assembly and secretion in goose primary hepatocytes

To investigate how cholesterol induces hepatocytic steatosis, we investigated the effect of cholesterol on hepatic lipogenesis and the assembly and secretion of very-low-density lipoprotein-triglycerides (VLDL-TGs) in goose primary hepatocytes. We found that cholesterol at 20 μg/ml increased the concentrations of extracellular VLDL, intracellular cholesterol, and intracellular TGs, while cholesterol at 30 μg/ml had a reduced effect (p < 0.05). Additionally, cholesterol at 20 μg/ml, but not at 10 or 30 μg/ml, increased the extracellular TG concentration. Cholesterol increased the fatty acid synthase (FAS) enzyme activity in a dose-dependent manner. Incubation with cholesterol increased the mRNA level of genes involved in lipogenesis, including sterol regulatory element-binding proteins (SREBPs), FAS, acetyl-CoA carboxylase-α (ACCα), and liver X receptors. The mRNA level of the acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) gene changed in response to cholesterol treatment in a dose-dependent manner. Similar to the regulation of extracellular VLDL and intracellular TG accumulation, the mRNA levels of the microsomal triglyceride transfer protein, forkhead box O1, and DGAT2 increased with treatment with 10 or 20 μg/ml of cholesterol, but decreased with treatment with 30 μg/ml of cholesterol (p < 0.05). Cholesterol had no evident effect on the mRNA level of the apolipoprotein B gene. Incubation with cholesterol at 20 and 30 μg/ml increased the nuclear SREBP-1 protein level (p < 0.05) and the binding affinity of the nuclear SREBP-1 to ACCα SRE probes. In conclusion, cholesterol not only activates the transcription of genes involved in fatty acid synthesis and TG accumulation, but also activates the transcription of genes involved in the assembly and secretion of VLDL-TG in goose primary hepatocytes.

VLDL triglycerides inhibit HDL-associated paraoxonase 1 (PON1) activity: in vitro and in vivo studies

We analyzed, for the first time, both in vitro and in vivo, the effect of very low density lipoprotein (VLDL), or of pure triglycerides, on high-density lipoprotein (HDL)-associated paraoxonase1 (PON1) catalytic activities. Incubation of serum or HDL from healthy subjects with VLDL (0-330 μg protein/mL) significantly decreased serum PON1 lactonase or arylesterase activities by up to 11% or 24%, and HDL-associated PON1 lactonase or arylesterase activities by up to 32% or 46%, respectively, in a VLDL dose-dependent manner. VLDL (0-660 μg protein/mL) also inhibited recombinant PON1 (rePON1) lactonase or arylesterase activities by up to 20% or 42%, respectively. Similar inhibitory effect was noted upon rePON1 incubation with pure triglyceride emulsion. Bezafibrate therapy to three hypertriglyceridemic patients (400 mg/day, for one month) significantly decreased serum triglyceride concentration by 67%, and increased serum HDL cholesterol levels by 48%. PON1 arylesterase or paraoxonase activities in the patients' HDL fractions after drug therapy were significantly increased by 86-88%, as compared to PON1 activities before treatment. Similarly, HDL-PON1 protein levels significantly increased after bezafibrate therapy. Finally, bezafibrate therapy improved HDL biological activity, as HDL obtained after drug therapy showed increased ability to induce cholesterol efflux from J774A.1 macrophages, by 19%, as compared to HDL derived before therapy. We thus conclude that VLDL triglycerides inhibit PON1 catalytic activities, and bezafibrate therapy significantly improved HDL-PON1 catalytic and biological activities.

Effect of mineralized water consumption on postprandial lipemia

Dietary factors may affect lipid metabolism and thus impact cardiovascular disease development. The objective of this study was to analyze the effects of 8 wk ingestion of mineralized water compared with control on fasting and postprandial lipoproteins levels in hyperlipidemic men. Subjects (N=12) consumed mineralized water (Saint Yorre) or low mineralized Water (Ogeu) in random order for 8‐wk periods, separated by a 1‐wk washout. Lipoprotein lipids were assessed prior to (fasting) and following a standard meal for 8 h (postprandial). Fasting and postprandial plasma triglycerides (TG) were decreased following mineralized water compared to control (p&lt;0.01 and &lt;0.05, respectively). This decrease was related to a significant decrease in fasting and postprandial levels of very low‐density lipoprotein (VLDL) TG (respectively p&lt;0.01 and p&lt;0.05) and a slight decrease in fasting total cholesterol (TC) (p&lt;0.1). High‐density lipoprotein cholesterol (HDL‐C) increased postprandially (p&lt;0.05) following the mineralized water compared to the low mineralized water. The reduction in postprandial concentrations of VLDL TG and the increase in HDL‐C suggest improvements in liver lipid metabolism and postprandial lipemia, which may favorably affect cardiovascular health.

Very Low Density Lipoprotein Metabolism in Patients with Chronic Kidney Disease

Background: Hypertriglyceridemia is a common metabolic complication of chronic kidney disease (CKD) and an important risk factor for coronary heart disease in this patient population. The mechanisms responsible for the development of hypertriglyceridemia in subjects with CKD are not clear. Methods: We studied very low density lipoprotein triglyceride (VLDL-TG) and VLDL-apolipoprotein B-100 (VLDL-apoB-100) kinetics in vivo in 6 subjects with non-dialysis-dependent CKD (CKD-ND), 6 subjects with CKD treated with peritoneal dialysis (CKD-PD) and 24 sex-, age- and body mass index-matched control subjects with normal renal function (12 control subjects each matched with the CKD-ND and CKD-PD group, respectively). Results: The secretion rates of VLDL-TG and VLDL-apoB-100 into plasma were not different between CKD-ND or CKD-PD and their respective control groups. The mean residence times of VLDL-TG and VLDL-apoB-100 in plasma, which represents the time VLDL-TG and VLDL-apoB-100 spend in the circulation after secretion by the liver, tended to be greater in subjects with CKD-ND than in control subjects (222 ± 38 vs. 143 ± 21 min, p = 0.07, and 352 ± 102 vs. 200 ± 20 min, p = 0.06, respectively) and were about two-fold greater in subjects with CKD-PD compared with their control group (248 ± 51 vs. 143 ± 21 min and 526 ± 116 vs. 182 ± 16 min, respectively; both p ≤ 0.01). Conclusion: Impaired plasma clearance of VLDL-TG and VLDL-apoB-100 is the major abnormality associated with hypertriglyceridemia in patients with either CKD-ND or CKD-PD.

Dyslipidemia in subclinical hypothyroidism and the effect of thyroxine on lipid profile

Introduction:Subclinical hypothyroidism (SH) has a prevalence between 4% and 10.5% in various studies. The burden of SH in India is expected to increase with increasing iodine sufficiency. Studies have shown conflicting results concerning not only the degree of lipid changes in SH but also the effect of thyroxine substitution therapy. Indian studies on dyslipidemia in SH and the effect of thyroxine on lipid profile are currently lacking.Aims and Objectives:(1) To assess the association of SH and lipid profile. (2) To quantify the effect of thyroxine treatment on lipid profile.Materials and Methods:About 54 patients who were detected to have SH were compared with 56 healthy controls. Thyroid stimulating hormone (TSH), free T3, free T4, anti thyroperoxidase (TPO) antibodies, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, Very low density lipoprotein (VLDL) cholesterol, serum triglycerides were measured in all the patients after an overnight fast. Selected patients were started on thyroxine replacement. Twenty-one patients were followed up after 3 months with a repeat lipid profile.Results:Mean total cholesterol and mean LDL levels were significantly higher in SH compared to controls, but there was no statistically significant difference in the mean HDL, VLDL, and triglyceride levels. There was a significant reduction in mean T. cholesterol, mean LDL, mean VLDL, and mean triglyceride levels after treatment with thyroxine, while there was no significant difference among the mean HDL levels.Conclusion:Dyslipidemia is more common in SH compared to controls. There is a TSH dependent increase in cholesterol, LDL, VLDL, and triglyceride levels. Achieving euthyroid status with thyroxine has a favourable effect on lipid profile.