Lipoprotein Lipase Mass Research Articles

Association between preheparin serum lipoprotein lipase mass and acute myocardial infarction in Japanese men.

A sensitive immunoassay system using a specific monoclonal antibody against lipoprotein lipase (LPL) recently demonstrated the presence of an LPL mass in preheparin serum. We reported that a preheparin serum LPL mass (pre-LPL mass) reflected the level of functioning LPL activity in the whole body and could be deeply involved in the progression of coronary atherosclerosis of stable organic angina pectoris. We examined the relation between the pre-LPL mass and acute myocardial infarction (AMI). We studied 44 males with AMI (AMI group) and 16 males with a normal coronary artery (NCA group), and measured the pre-LPL mass by enzyme-linked immunosorbent assay. Coronary risk factors including the pre-LPL mass were compared between the two groups and multiple regression analysis was performed for AMI. There were no significant differences in the lipid data, but the pre-LPL mass level was significantly low in the AMI group (52 +/- 16 vs 41 +/- 14 ng/ml, p = 0.01), and a low pre-LPL mass concentration was observed in the small sized LDL group and/or the Midband positive group. Multiple regression analysis revealed that a low pre-LPL mass and hypertriglyceridemia were independent risk factors for AMI (t value = 2.1, 2.4). The result indicates that a low pre-LPL mass may be an important risk factor for AMI and stable organic angina pectoris.

Reduction of plasma triglyceride level and enhancement of plasma albumin concentration by Oren-gedoku-to administration.

Oren-gedoku-to (Huanglian-Jie-Du-Tang, OGT) has been used for the treatment of cerebrovascular disease, hypertension, gastritis and liver disease in Japan. The present study was to test whether ingestion of OGT extract (TJ-15) would affect the metabolism of fatty acids and the usual antioxidant molecule (such as albumin, uric acid and bilirubin) levels in human plasma. After the administration of TJ-15, plasma total cholesterol and the triglyceride level significantly decreased, and lipoprotein lipase mass increased. Significant enhancement of plasma albumin level and reduction of the total plasma protein level resulted in an increment of the albumin/globulin ratio. Plasma fibrinogen, an independent risk factor for cerebrovascular disease, declined considerably, but the reduction was not statistically significant. The findings of this study suggest that ingestion of TJ-15 improves the microcirculation through lipid and protein metabolisms, and is useful for the treatment of cerebral vascular attack in human.

Effect of atorvastatin treatment on lipoprotein lipase mass in the pre-heparin plasma in Japanese hyperlipidemic subjects

Background: Atorvastatin is a recently introduced statin that lowers LDL-cholesterol (LDL-C) and triglycerides more than some of the older statins. Methods: Twenty-one Japanese hyperlipidemic subjects were treated with atorvastatin (10 mg/day) for 6 weeks. Plasma lipid concentrations and pre-heparin plasma LPL mass before and after oral administration were evaluated using an open crossover trial format. LPL mass in the pre-heparin plasma was measured by a sandwich enzyme immunoassay. Results: Atorvastatin decreased plasma triglyceride (TG) concentration (−21%, p<0.05), as well as plasma total and LDL-cholesterol concentrations. LPL mass in the pre-heparin plasma did not change significantly by this treatment during this period. Both apolipoprotein (apo) B and E decreased considerably (−33%, p<0.001 for apo B; −29% p<0.001 for apo E), while apo A-I concentration did not change. Other clinical parameters such as body mass index, blood pressure, and fasting plasma glucose concentration of these subjects did not change during this treatment. Conclusions: Atorvastatin is effective in reducing plasma TG, which did not appear to be associated with an increased LPL mass.

A family-based study of hyperinsulinemia and hypertriglyceridemia in heterozygous lipoprotein lipase deficiency

Case report: A case is presented of predisposing a patient's father with obligate heterozygous lipoprotein lipase (LPL) deficiency to mild hypertriglyceridemia in Japanese I-family members ( n=8) with patient DI, who was a compound heterozygote for a novel missense mutation of G154V (G G 716C→G T C/Gly 154 Val) in exon 5 and a novel splice mutation (Int8/5′-dss/t(+2)c; a T-to-C transition in the invariant GT at position +2 of the 5′ donor splice site (dss)) in intron 8 of the LPL gene. Results: The patient's father and paternal grandmother were heterozygotes for the Int8/5′-dss/t(+2)c allele, while the patient's mother and maternal grandmother were heterozygotes for the G154V allele. These four heterozygous carriers with one defective LPL allele showed 45–57% of the mean LPL activity and mass in the post-heparin plasma (PHP) observed in normal individuals. Among the four heterozygous carriers, the patient's father, who was <40 years old, nonobese and hyperinsulinemia, manifested mild hypertriglyceridemia (type IV hyperlipoproteinemia). The remaining three healthy heterozygous carriers (two were >40 years old and the other was <40 years old) were all normolipidemic state. Conclusion: In this family, hyperinsulinemia as a marker of insulin resistance may be a strong determinant of hypertriglyceridemia in the carrier with heterozygous LPL deficiency.

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

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate gene expression of lipoprotein lipase (LPL) in liver and adipose tissue. We examined the direct effect of PPAR-alpha ligands on LPL catalytic activity in cultured cardiomyocytes from adult rat heart. After overnight culture (16 h), 1 microM Wy-14643 and 10 microM BM-17.0744 decreased total cellular LPL activity to approximately 50% of control with no change in enzyme synthesis or mass; as a consequence, PPAR-alpha activation produced a significant decrease in LPL specific activity (mU/ng LPL protein). Wy-14643 and BM-17.0744 also reduced heparin-releasable LPL activity and mass in the culture medium. Inhibition of LPL activity by Wy-14643 did not reduce the ability of insulin plus dexamethasone to stimulate cellular and heparin-releasable LPL activities. A similar inhibitory effect on cellular and heparin-releasable LPL activity was observed when cardiomyocytes were cultured with 60 microM linoleic acid. In conclusion, two different PPAR-alpha ligands (Wy-14643 and BM-17.0744) inhibited cellular LPL activity in cultured cardiomyocytes by a posttranscriptional and posttranslational mechanism.

Direct regulatory effect of fatty acids on macrophage lipoprotein lipase: potential role of PPARs.

Atherosclerosis is a major complication of type 2 diabetes. The pathogenesis of this complication is poorly understood, but it clearly involves production in the vascular wall of macrophage (Mo) lipoprotein lipase (LPL). Mo LPL is increased in human diabetes. Peripheral factors dysregulated in diabetes, including glucose and free fatty acids (FAs), may contribute to this alteration. We previously reported that high glucose stimulates LPL production in both J774 murine and human Mo. In the present study, we evaluated the direct effect of FAs on murine Mo LPL expression and examined the involvement of peroxisome proliferator-activated receptors (PPARs) in this effect. J774 Mo were cultured for 24 h with 0.2 mmol/l unsaturated FAs (arachidonic [AA], eicosapentaenoic [EPA], and linoleic acids [LA]) and monounsaturated (oleic acid [OA]) and saturated FAs (palmitic acid [PA] and stearic acid [SA]) bound to 2% bovine serum albumin. At the end of this incubation period, Mo LPL mRNA expression, immunoreactive mass, activity, and synthetic rate were measured. Incubation of J774 cells with LA, PA, and SA significantly increased Mo LPL mRNA expression. In contrast, exposure of these cells to AA and EPA dramatically decreased this parameter. All FAs, with the exception of EPA and OA, increased extra- and intracellular LPL immunoreactive mass and activity. Intracellular LPL mass and activity paralleled extracellular LPL mass and activity in all FA-treated cells. In Mo exposed to AA, LA, and PA, an increase in Mo LPL synthetic rate was observed. To evaluate the role of PPARs in the modulatory effect of FAs on Mo LPL gene expression, DNA binding assays were performed. Results of these experiments demonstrate an enhanced binding of nuclear proteins extracted from all FA-treated Mo to the peroxisome proliferator-response element (PPRE) consensus sequence of the LPL promoter. PA-, SA-, and OA-stimulated binding activity was effectively diminished by immunoprecipitation of the nuclear proteins with anti-PPAR-alpha antibodies. In contrast, anti-PPAR-gamma antibodies only significantly decreased AA-induced binding activity. Overall, these results provide the first evidence for a direct regulatory effect of FAs on Mo LPL and suggest a potential role of PPARs in the regulation of Mo LPL gene expression by FAs.

Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis

In preheparin serum, there exists lipoprotein lipase (LPL) mass with little activity. The clinical significance of this preheparin serum LPL mass (preheparin LPL mass) is unclear. We studied the levels of preheparin LPL mass in patients with coronary atherosclerosis, comparing the results with those in healthy men. We also evaluated the correlation between preheparin LPL mass and the severity of coronary atherosclerosis by comparing with other risk factors such as age, smoking, family history, hypertension, hyperuricemia, diabetes mellitus, total cholesterol, triglyceride, high density lipoprotein-cholesterol and body mass index. The subjects, 70 men presenting with symptoms of coronary artery disease, underwent coronary angiographic examination. Significant narrowness was defined as≥75%. Control group comprised 77 men who had annual health checks and showed no abnormal findings. Preheparin LPL mass in the stenosis group was lower than normal coronary group and also than the control group. Multivariate analysis showed that preheparin LPL mass had the highest t-value (−2.53) for the number of lesions among the risk factors listed above. These results suggest that low preheparin LPL mass may be deeply involved in the progression of coronary atherosclerosis.

A compound heterozygote for a novel missense mutation (G105R) in exon 3 and a missense mutation (D204E) in exon 5 of the lipoprotein lipase gene in a Japanese infant with hyperchylomicronaemia

We systematically investigated the molecular defects resulting in primary lipoprotein lipase (LPL) deficiency in a Japanese male infant (hereafter called 'the patient') with severe fasting hypertriglyceridaemia (type I hyperlipoproteinaemia). The primary LPL deficiency was diagnosed on the basis of the findings that no LPL activity was detected in post-heparin plasma (PHP) and that the immunoreactive LPL mass in PHP was less than 2% of the control level. The patient was a compound heterozygote for a novel missense mutation (G(568)GA-->AGA/Gly(105)-->Arg; G105R) in exon 3 and a missense mutation (GAC(867)-->GAG/Asp(204)-->Glu; D204E) in exon 5 of the LPL gene. The biological significance of both missense mutations was examined by an in vitro study of the expression of the mutant G105R LPL cDNA and D204E LPL cDNA in COS-1 cells. Both mutant LPLs were catalytically inactive and were barely released by heparin from the expressing COS-1 cells. These findings explain the failure to detect LPL activity and immunoreactive LPL mass in the patient's PHP. The G105R allele could be detected by digestion with the BsmAI restriction enzyme, and the D204E allele by digestion with HincII. The patient inherited the G105R allele from his mother and the D204E allele from his father. His parents were heterozygotes for the corresponding mutant allele, but normolipidaemic. The novel G105R missense mutation could not be detected by conventional analysis of single-strand conformation polymorphism, but it was identified by extensive sequencing of the entire exons and their flanking regions in the LPL gene.

A newly identified lipoprotein lipase (LPL) gene mutation (F270L) in a Japanese patient with familial LPL deficiency

We have systematically investigated the molecular defects resulting in a primary lipoprotein lipase (LPL) deficiency in a Japanese male infant (proband SH) with fasting hyperchylomicronemia. Neither LPL activity nor immunoreactive LPL mass was detected in pre- or postheparin plasma from proband SH. DNA sequence analysis of the LPL gene of proband SH revealed homozygosity for a novel missense mutation of F270L (Phe 270→Leu/TT T 1065→TT G ) in exon 6. The function of the mutant F270L LPL was determined by both biochemical and immunocytochemical studies. In vitro expression experiments on the mutant F270L LPL cDNA in COS-1 cells demonstrated that the mutant LPL protein was synthesized as a catalytically inactive form and its total amount was almost equal to that of the normal LPL. Moreover, the synthesized mutant LPL was non-releasable by heparin because the intracellular transport of the mutant LPL to the cell surface – by which normal LPL becomes heparin-releasable – was impaired due to the abnormal structure of the mutant LPL protein. These findings explain the failure to detect LPL activities and masses in pre- and postheparin plasma of the proband. The mutant F270L allele generated an XcmI restriction enzyme site in exon 6 of the LPL gene. The carrier status of F270L in the proband’s family members was examined by digestion with XcmI. The proband was ascertained to be homozygous for the F270L mutation and his parents and sister were all heterozygous. The LPL activities and masses of the parents and the sister (carriers) were half or less than half of the control values. Regarding the phenotype of the carriers, the mother with a sign of hyperinsulinemia manifested hypertriglyceridemia (type IV hyperlipoproteinemia), whereas the healthy father and the sister were normolipidemic. Hyperinsulinemia may be a strong determinant of hypertriglyceridemia in subjects with heterozygous LPL deficiency.

Enhancement of preheparin serum lipoprotein lipase mass by bezafbirate administration

To clarify the clinical implication of preheparin serum lipoprotein lipase mass (preheparin LpL mass), we studied the relationships between preheparin LpL mass and serum lipids, including midband lipoproteins, which migrate between very low density lipoproteins and low density lipoproteins on polyacrylamide gel disc electrophoresis, in hyperlipidemias. And we also studied the changes of preheparin LpL mass in hypertriglyceridemic patients during bezafibrate administration, which is known to enhance LpL activity in postheparin plasma. Preheparin LpL mass correlated positively with high-density lipoprotein-cholesterol (HDL-C) ( r=0.418, P<0.01) and negatively with triglyceride (TG) ( r=−0.256, P<0.01), but did not correlate with total cholesterol (TC) in 64 hyperlipidemic (type IIa, IIb and IV) patients. The midband lipoproteins were observed in 80% of hypertriglyceridemic patients (32/40). Preheparin LpL mass in midband lipoprotein-positive subjects was lower significantly than that in midband-negative subjects. When bezafibrate (400 mg/day) was administrated to 40 hypertriglyceridemic patients for 4 months, TG level significantly decreased (−49±7%, P<0.01), TC levels decreased (−11±4%, not significant), and HDL-C levels increased (+27±4%, P<0.01). The midband lipoproteins disappeared in 95% of patients. Preheparin LpL mass significantly increased (+25±6%, P<0.0005). In nine patients who stopped bezafibrate, TG levels significantly increased (+49±7%, P<0.01) and HDL-C levels decreased (−27±4%, P<0.01). Preheparin LPL mass significantly decreased (−25±6%, P<0.0005). These results suggested that bezafibrate administration enhanced preheparin LpL mass. And it might be implicated that enhanced LpL production by bezafibrate could reflect an increase of preheparin LpL mass.

Differential Expression of Lipoprotein Lipase Gene in Tissues of the Rat Model with Visceral Obesity and Postprandial Hyperlipidemia

Postprandial hyperlipidemia is frequently accompanied with intra-abdominal visceral accumulation in human subjects. We have found that the decreased lipoprotein lipase (LPL) mass and activity is negatively associated with the amount of visceral fat accumulation. Here, we studied the postprandial hyperlipidemia using the OLETF rat, a model with visceral obesity, in order to clarify the molecular mechanism causing postprandial hyperlipidemia accompanied with visceral obesity. At the same age of 32 weeks, the OLETF rats showed obviously higher plasma leptin, total cholesterol, triglyceride, and HDL-cholesterol levels than the control LETO rats, although the plasma glucose level was not significantly different. Fat-loading test revealed the delayed metabolism of exogenous fat in the OLETF rats compared to the LETO rats, similar to human subjects with visceral obesity. In the obese rats, plasma levels of LPL mass and activities were 60 and 49% of control rats. The expression of LPL gene was decreased in subcutaneous adipose tissues and skeletal muscle of OLETF rats to 40 and 52% compared to those of LETO rats. In OLETF rats, plasma tumor necrosis factor-alpha (TNF-α) and insulin levels were increased to 2.0- and 2.3-folds compared to those in control rats. Furthermore, plasma insulin and TNF-α levels in OLETF rats were negatively correlated with the expression levels of LPL gene in subcutaneous fat and muscle. These results indicate that decreased LPL mass and activity in the animal model with visceral obesity is possibly caused by decreased expression of LPL gene in tissues mediated by the increased levels of insulin and TNF-α. The different expression of LPL gene in tissues associated with the increased levels of insulin and TNF-α possibly elucidate the underlying mechanisms involving the postprandial hyperlipidemia observed in visceral obesity.

Preheparin lipoprotein lipase mass might be reflecting the amount of produced lipoprotein lipase in the whole body

Preheparin lipoprotein lipase mass might be reflecting the amount of produced lipoprotein lipase in the whole body

CHRONIC HEPATITIS C BETA‐INTERFERON‐INDUCED SEVERE HYPERTRIGLYCERIDAEMIA WITH APOLIPOPROTEIN E PHENOTYPE E3/2

SUMMARYThe mechanisms of hypertriglyceridaemia and changes in plasma lipoprotein subfractions by β‐interferon treatment were studied in a hepatitis C patient with apo E phenotype E3/2. Plasma levels of triglyceride (TG) were increased by treatment with 6 × 106 β‐interferon and reached 8.06 mmol/l at 4 weeks of treatment. Low energy and low fat diet reduced them to half the maximal level. Plasma levels of LDL1 (1.019&lt;d&lt;1.045)‐C, LDL2 (1.045&lt;d&lt;1.063)‐C, HDL2‐C and HDL3‐C were 0.39, 0.31, 0.21 and 0.28 mmol/l, respectively, which are low, but the plasma levels of IDL, which is a remnant of TG‐rich lipoproteins, was normal at 7 weeks of treatment. The distribution of plasma lipoprotein subfractions returned to normal after interferon treatment was discontinued. The mass and activity of lipoprotein lipase (LPL) were reduced to half the baseline level by interferon treatment. The activity of hepatic triglyceride lipase (HTGL) which transforms IDL to LDL was normal. The patient's apo E phenotype was E3/2; with that phenotype the removal of TG‐rich lipoproteins and IDL through the receptors of the remnant and LDL is impaired. But the IDL plasma level was normal, probably because of normal HTGL activity and high LDL‐receptor activity. Lymphocyte LDL‐receptor activity was double that of the control. We conclude that interferon caused the low mass and activity of LPL which in turn caused the hypertriglyceridaemia. And no retention of the remnant of TG‐rich lipoproteins in this patient with apo E3/2 and low levels of LDL subfractions was due to the active removal of them through LDL‐receptors as well as the impaired production of them by suppression of LPL by interferon. (Int J Clin Pract 2000; 54(4): 212‐216)

Upregulation of macrophage lipoprotein lipase in patients with type 2 diabetes: role of peripheral factors.

Atherosclerosis is the major complication of diabetes. Accumulating evidence indicates that lipoprotein lipase (LPL) produced by macrophages in the vascular wall may favor the development of atherosclerosis by promoting lipid accumulation within the lesion. We previously demonstrated that high glucose stimulates in vitro murine and human macrophage LPL production. In this study, we measured macrophage LPL mRNA expression, immunoreactive mass, and activity in normotriglyceridemic subjects with type 2 diabetes. Monocytes isolated from healthy control subjects and patients with type 2 diabetes were differentiated into macrophages in RPMI medium containing 20% autologous serum. After 5 days in culture, macrophage LPL mRNA expression, mass, and activity were determined. Macrophages of diabetic patients cultured in their own sera showed a significant increase in LPL mRNA levels, mass, and activity compared with macrophages of control subjects. Differentiation of macrophages of diabetic patients in sera obtained from control subjects significantly reduced these anomalies. Conversely, culturing macrophages of control subjects in sera of diabetic patients significantly increased LPL mass and activity in these cells. Besides LPL overproduction, macrophages of diabetic patients exhibited an increase in basal and LPL-induced tumor necrosis factor (TNF)-alpha release. TNF-alpha alterations were reduced by exposing these cells to sera of control subjects. Overall, these data demonstrate that macrophages of diabetic patients overexpress LPL and TNF-alpha and that peripheral factors dysregulated in diabetes are, at least in part, responsible for these alterations.

Marked decrease in plasma apolipoprotein A-I and high density lipoprotein-cholesterol in a case with Werner syndrome

The patient was a 39-year-old Japanese male with a body height of 160 cm and weight of 48 kg who was diagnosed as Werner syndrome of homozygote for mutation 4. His plasma total cholesterol (TC), triglycerides (TGs), high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) levels were 7.2, 2.1, 1 mmol/l and 128 mg/dl, respectively. During the clinical course of treatment of this patient, his plasma levels of HDL-C and apo A-I declined drastically to levels of as low as 0.2 mmol/l and 10 mg/dl, respectively, with concurrent reciprocal increase in plasma TG levels. Plasma HDL-C, apo A-I and TG levels gradually returned to original values. Lipoprotein lipase activity and mass in post-heparin plasma were markedly low when the apo A-I and HDL-C levels decreased to 10 mg/dl and 0.21 mmol/l, respectively, and these values improved when the apo A-I and HDL-C levels returned to more normal values of 106 mg/dl and 0.94 mmol/l, respectively. The result of direct sequence of the exon 3 and 4, and the promoter region of the apo A-I gene of the patient revealed no single nucleotide changes. These results suggest that in the present patient, impaired hydrolysis of TGs in TG-rich lipoproteins, is due at least in part to a decreased LPL enzyme level, reduced the formation of nascent HDL, resulting in unusually low plasma levels of HDL-C and apo A-I.

Compound heterozygosity of Leu252Val and Leu252Arg causing lipoprotein lipase deficiency in a chinese patient with hypertriglyceridemia.

We investigated lipoprotein lipase (LPL) gene mutations in a Chinese male with severe hypertriglyceridemia and recurrent pancreatitis. We screened for LPL sequence mutation in the LPL gene in this patient, his relatives and 160 unrelated hypertriglyceridaemic subjects. We determined the postheparin plasma LPL activity of subjects carrying a LPL mutation and studied the in vitro expression of mutant LPL in COS-1 cells. The proband was found to be a compound heterozygote for a novel Leu252Val and a reported Leu252Arg mutation in the LPL gene. He had low plasma levels of postheparin LPL activity and mass. The two mutations segregated independently in his family. In vitro expression analysis showed that Leu252Arg abolished both the catalytic function and secretion of LPL, while Leu252Val abolished the catalytic function but only reduced secretion by about half. We have also detected heterozygous Leu252Val and Leu252Arg mutations each in one hypertriglyceridaemic individual. These results indicated that the leucine 252 is critical for the catalytic activity and secretion of LPL. Why the substitution by valine instead of arginine resulted only in a partial suppression of LPL secretion, remains to be investigated. Leu252Val and Leu252Arg are the likely cause of hypertriglyceridemia in these subjects because of their deleterious effects on LPL activity or secretion. Leu252Val/Leu252Arg is the first compound heterozygous mutation known to occur in the same codon of the LPL gene. So far they are found only in Chinese.

The effect of insulin sensitizer, troglitazone, on lipoprotein lipase mass in preheparin serum

Lipoprotein lipase mass exists in preheparin serum, even though the activity is scarcely found. The implication of this is unclear. We studied the effect of an insulin sensitizer, troglitazone, on this preheparin serum lipoprotein lipase mass (preheparin LPL mass) in non-insulin-dependent diabetes mellitus (NIDDM) patients as well as on serum lipid levels and low density lipoproteins (LDL) particle size. Thirty-one NIDDM patients with poor control were administered troglitazone 400 mg/day. Hemoglobin A1c had significantly decreased (13%, P<0.001) 2 months later. Preheparin LPL mass had gradually increased and a 69% increase ( P<0.01) was observed 4 months later. Triglyceride significantly decreased (23%, P<0.01) and high density lipoprotein-cholesterol increased (10%, P<0.0l), whereas total cholesterol and LDL levels did not change 4 months later. The size of LDL increased significantly ( P<0.01). These results were consistent with the idea that preheparin LPL mass might be relating to the insulin sensitivity enhanced by troglitazone, as well as LDL particle size.

Role of hepatic lipase in intermediate-density lipoprotein and small, dense low-density lipoprotein formation in hemodialysis patients

It has been reported that remnant lipoproteins and small, dense low-density lipoproteins (LDLs) are risk factors for cardiovascular disease. To determine whether these risk factors are present in hemodialysis (HD) patients who are suffering from a high incidence of atherosclerotic vascular disease, we measured concentrations of remnant lipoproteins and LDL particle diameter in HD patients and compared these with controls. We also measured lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) that play important roles in the generation of remnant lipoproteins and small, dense LDL, and we correlated these changes with plasma lipoprotein abnormalities in HD patients. Lipoproteins were separated by ultracentrifugation. Apoprotein B in very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) fractions were measured by a sensitive enzyme-linked immunosorbent assay method. The average LDL particle diameter was measured by gradient gel electrophoresis. Plasma triglyceride, total cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations were comparable between HD patients and controls, whereas LDL cholesterol was significantly lower in HD patients. The average LDL particle diameter was not significantly different between HD patients and controls. LDL particle diameter was inversely related to plasma triglyceride concentrations in all of the subjects. VLDL triglyceride, VLDL cholesterol, and VLDL apoprotein B were comparable between HD patients and controls. IDL triglyceride, IDL cholesterol, and IDL apoprotein B concentrations were all significantly increased in HD patients compared with those in controls. LPL mass was not altered, but HTGL activity was significantly decreased in HD patients. The HTGL activity was inversely related to IDL concentrations. These results suggest that a prominent characteristic of lipoprotein abnormalities in HD patients is a marked increase in IDL particle number. In addition, small, dense LDL is not associated with uremic dyslipidemia. Because HTGLs promote the conversion from IDL to LDL and the generation of lipid-poor LDL, a decrease in HTGL activity may contribute to the accumulation of IDL particle and may prevent small, dense LDL formation in HD patients.

Lipoprotein abnormalities in diabetic nephropathy

The risk of death from coronary heart disease (CHD) is substantially increased in diabetic nephropathy compared with normal subjects or diabetes without nephropathy. I tried to define abnormal plasma lipoproteins profiles contributing to the increased CHD risk in diabetic nephropathy. This study included: middle-aged to older type 2 diabetic patients with normoalbuminuria, microalbuminuria, and overt albuminuria; nondiabetic patients with primary renal disease; and normal control subjects. Triglyceride (TG) levels were significantly increased in type 2 diabetic patients with microalbuminuria and overt proteinuria. Glycemic control or insulin resistance were not associated with TG levels. Intermediate-density lipoprotein (IDL) and remnant-like particle (RLP) cholesterol in type 2 diabetics were significantly elevated in patients with overt nephropathy. Hepatic TG lipase (HTGL) was significantly decreased in diabetic nephropathy, and their higher IDL levels were inversely related to decreased HTGL. Low-density lipoprotein (LDL) size was significantly smaller in diabetic nephropathy compared with nondiabetics with kidney disease. The TG response after the oral fat load was significantly greater in diabetic nephropathy, and the LDL size was inversely associated with the magnitude of postprandial lipemia. Microalbuminuric diabetic patients had a lower lipoprotein lipase (LPL) mass and a higher von Willebrand factor (vWF), an indicator of endothelial cell damage, than normoalbuminuric patients. The LPL mass was inversely associated with vWF, suggesting that widespread endothelial cell damage results in a reduction in LPL bound to endothelium in diabetic subjects with microalbuminuria. Plasma lipoprotein profiles become more atherogenic in patients with diabetic nephropathy, including the subclinical stage, compared with diabetics without nephropathy or those with nondiabetic kidney disease.

Identification of compound heterozygous mutations (G188E/W382X) of lipoprotein lipase gene in a Japanese infant with hyperchylomicronemia:: the G188E mutation was newly identified in Japanese

We herein report a case of a 5-month-old Japanese female (patient AN) with fasting hyperchylomicronemia due to a primary lipoprotein lipase (LPL) deficiency. Patient AN was compound heterozygous for a missense mutation (G G 818G→G A G/Gly 188→Glu; G188E) in exon 5 and a nonsense mutation (TG G 1401→TG A /Trp 382→Stop; W382X) in exon 8 of the LPL gene. This resulted in less than 10% of the control levels for both the LPL activity and immunoreactive LPL mass in the postheparin plasma. A G188E mutation was thus identified for the first time in a Japanese, and the haplotype of this G188E allele was different from that of the G188E alleles identified in other ethnic groups. This additional mutation might be useful for early diagnosis of LPL gene aberrations in Japanese patients with fasting hyperchylomicronemia.