Low-density and high-density lipoprotein subspecies and risk for premature coronary artery disease.
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Age of Onset↗
Biomedical subjects
J D Brunzell
Publications and source records attributed to J D Brunzell.
Evidence for a new pathophysiological mechanism for coronary artery disease regression: hepatic lipase-mediated changes in LDL density.
BACKGROUND: Small, dense LDL particles are associated with coronary artery disease (CAD) and predict angiographic changes in response to lipid-lowering therapy. Intensive lipid-lowering therapy in the Familial Atherosclerosis Treatment Study (FATS) resulted in significant improvement in CAD. This study examines the relationship among LDL density, hepatic lipase (HL), and CAD progression, identifying a new biological mechanism for the favorable effects of lipid-altering therapy. METHODS AND RESULTS: Eighty-eight of the subjects in FATS with documented coronary disease, apolipoprotein B levels >/=125 mg/dL, and family history of CAD were selected for this study. They were randomly assigned to receive lovastatin (40 mg/d) and colestipol (30 g/d), niacin (4 g/d) and colestipol, or conventional therapy with placebo alone or with colestipol in those with elevated LDL cholesterol levels. Plasma hepatic lipase (HL), lipoprotein lipase, and LDL density were measured when subjects were and were not receiving lipid-lowering therapy. LDL buoyancy increased with lovastatin-colestipol therapy (7.7%; P<0.01) and niacin-colestipol therapy (10.3%; P<0.01), whereas HL decreased in both groups (-14% [P<0.01] and -17% [P<0.01] with lovastatin-colestipol and niacin-colestipol, respectively). Changes in LDL buoyancy and HL activity were associated with changes in disease severity (P<0.001). In a multivariate analysis, an increase in LDL buoyancy was most strongly associated with CAD regression, accounting for 37% of the variance of change in coronary stenosis (P<0.01), followed by reduction in apolipoprotein Bl (5% of variance; P<0.05). CONCLUSIONS: These studies support the hypothesis that therapy-associated changes in HL alter LDL density, which favorably influences CAD progression. This is a new and potentially clinically relevant mechanism linking lipid-altering therapy to CAD improvement.
Aged↗
Linkage of low-density lipoprotein size to the lipoprotein lipase gene in heterozygous lipoprotein lipase deficiency.
Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in the LpL gene. LDL particle size was smaller among the heterozygous subjects, compared with controls. Among heterozygous subjects, 44% were classified as affected by LDL subclass phenotype B, compared with 8% of normal family members. Plasma triglyceride levels were significantly higher, and high-density lipoprotein cholesterol (HDL-C) levels were lower, in heterozygous subjects, compared with normal subjects, after age and sex adjustment. A highly significant LOD score of 6.24 at straight theta=0 was obtained for linkage of LDL particle size to the LpL gene, after adjustment of LDL particle size for within-genotype variance resulting from triglyceride and HDL-C. Failure to adjust for this variance led to only a modest positive LOD score of 1.54 at straight theta=0. Classifying small LDL particles as a qualitative trait (LDL subclass phenotype B) provided only suggestive evidence for linkage to the LpL gene (LOD=1. 65 at straight theta=0). Thus, use of the quantitative trait adjusted for within-genotype variance, resulting from physiologic covariates, was crucial for detection of significant evidence of linkage in this study. These results indicate that heterozygous LpL deficiency may be one cause of small LDL particles and may provide a potential mechanism for the increase in coronary disease seen in heterozygous LpL deficiency. This study also demonstrates a successful strategy of genotypic specific adjustment of complex traits in mapping a quantitative trait locus.
Adolescent↗
A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women.
High hepatic lipase (HL) activity is associated with an atherogenic lipoprotein profile of small, dense LDL particles and lower HDL(2)-C. Intra-abdominal fat (IAF) is positively associated with HL activity. A hepatic lipase gene (LIPC) promoter variant (G-->A(-250)) is associated with lower HL activity, higher HDL(2)-C, and less dense LDL particles. To determine whether the LIPC promoter polymorphism acts independently of IAF to regulate HL, 57 healthy, premenopausal women were studied. The LIPC promoter A allele was associated with significantly lower HL activity (GA/AA=104+/-34 versus GG=145+/-57 nmoles x mL(-1) x min(-1), P=0.009). IAF was positively correlated with HL activity (r=0.431, P<0.001). Multivariate analysis revealed a strong relationship between both the LIPC promoter genotype (P=0. 001) and IAF (P<0.001) with HL activity. The relationship between IAF and HL activity for carriers and noncarriers of the A allele was curvilinear with the carriers having a lower apparent maximum level of plasma HL activity compared with noncarriers (138 versus 218 nmoles x mL(-1) x min(-1), P<0.001). In addition, the LIPC A allele was associated with a significantly higher HDL(2)-C (GA/AA=16+/-7 versus GG=11+/-5 mg/dL, P=0.003). We conclude that the LIPC promoter A allele attenuates the increase in HL activity due to IAF in premenopausal women.
Abdomen↗
Mutations in the lipoprotein lipase gene associated with ischemic heart disease in men. The Copenhagen city heart study.
The aim of this study was to test the hypothesis that the Asp9Asn substitution and the T(-93)-->G mutation in the promoter of the lipoprotein lipase gene affect plasma lipid levels and thereby the risk of ischemic heart disease (IHD). We genotyped 9033 men and women from a general population sample and 940 patients with IHD. The frequency of both the G allele and the Asn9 allele in the general population sample was approximately 0.015 for both men and women. These 2 mutations appeared together in 95% of carriers. The average triglyceride-raising effect associated with double heterozygosity for the T(-93)-->G mutation and the Asp9Asn substitution was 0.28 mmol/L (P=0.004) and 0.16 mmol/L (P=0.10) in men and women, respectively. On logistic regression analysis allowing for age, the risk of IHD for double heterozygous men and women was increased 90% (95% confidence interval [CI], 20% to 200%) and 30% (95% CI, -40% to 170%), respectively, compared with noncarriers. When, in addition, other conventional cardiovascular risk factors were allowed for, the risk of IHD for double heterozygous men and women was increased 70% (95% CI, 0% to 190%) and 20% (95% CI, -50% to 180%), respectively. Of the overall risk of IHD in men in the general population, the fraction attributable to double heterozygosity was 3%, similar to the 5% attributable to diabetes mellitus. These results demonstrate that the Asp9Asn substitution is in linkage disequilibrium with the T(-93)-->G mutation and that the double-heterozygous carrier status is associated with elevated plasma triglycerides and an increased risk of IHD in men.
Adult↗
Increased small dense LDL and intermediate-density lipoprotein with albuminuria in type 1 diabetes.
OBJECTIVE: This population study examines the relationship between LDL density and persistent albuminuria in subjects with type 1 diabetes at the end of the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS: Subjects were classified as persistently normoalbuminuric (albumin excretion rate [AER] < 30 mg/d, n = 1,056), microalbuminuric (AER > or = 30-299 mg/day, n = 80), and macroalbuminuric (AER = 300 mg/day, n = 24) based on the last two AER measures. RESULTS: Triglyceride (P < 0.01) and LDL cholesterol (P < 0.01) levels were higher in macroalbuminuric subjects compared with normoalbuminuric subjects. Cholesterol distribution by density-gradient ultracentrifugation showed an increase in intermediate-density lipoprotein (IDL) and a shift in peak LDL from buoyant toward more dense particles with progressive albuminuria. In the entire group, there was a significant negative correlation between the peak buoyancy of LDL particles and albuminuria (r = -0.238, P < 0.001, n = 1,160). This correlation persisted in the normoalbuminuric DCCT group (r = -0.138, P < 0.001, n = 1,056). CONCLUSIONS: As albuminuria increases in subjects with type 1 diabetes, dyslipidemia occurs with an increase in IDL and dense LDL that may lead to increased cardiovascular disease.
Adolescent↗
Dyslipidemia of central obesity and insulin resistance.
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Coronary Disease↗
Catalytically inactive lipoprotein lipase expression in muscle of transgenic mice increases very low density lipoprotein uptake: direct evidence that lipoprotein lipase bridging occurs in vivo.
Lipoprotein lipase (LPL) is the central enzyme in plasma triglyceride hydrolysis. In vitro studies have shown that LPL also can enhance lipoprotein uptake into cells via pathways that are independent of catalytic activity but require LPL as a molecular bridge between lipoproteins and proteoglycans or receptors. To investigate whether this bridging function occurs in vivo, two transgenic mouse lines were established expressing a muscle creatine kinase promoter-driven human LPL (hLPL) minigene mutated in the catalytic triad (Asp156 to Asn). Mutated hLPL was expressed only in muscle and led to 3,100 and 3,500 ng/ml homodimeric hLPL protein in post-heparin plasma but no hLPL catalytic activity. Less than 5 ng/ml hLPL was found in preheparin plasma, indicating that proteoglycan binding of mutated LPL was not impaired. Expression of inactive LPL did not rescue LPL knock-out mice from neonatal death. On the wild-type (LPL2) background, inactive LPL decreased very low density lipoprotein (VLDL)-triglycerides. On the heterozygote LPL knock-out background (LPL1) background, plasma triglyceride levels were lowered 22 and 33% in the two transgenic lines. After injection of radiolabeled VLDL, increased muscle uptake was observed for triglyceride-derived fatty acids (LPL2, 1.7x; LPL1, 1.8x), core cholesteryl ether (LPL2, 2.3x; LPL1, 2.7x), and apolipoprotein (LPL1, 1.8x; significantly less than cholesteryl ether). Skeletal muscle from transgenic lines had a mitochondriopathy with glycogen accumulation similar to mice expressing active hLPL in muscle. In conclusion, it appears that inactive LPL can act in vivo to mediate VLDL removal from plasma and uptake into tissues in which it is expressed.
Animals↗
Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. Diabetes Control and Complications Trial.
CONTEXT: Intensive treatment of type 1 diabetes results in greater weight gain than conventional treatment. OBJECTIVE: To determine the effect of this weight gain on lipid levels and blood pressure. DESIGN: Randomized controlled trial; ancillary study of the Diabetes Control and Complications Trial (DCCT). SETTING: Twenty-one clinical centers. PARTICIPANTS: The 1168 subjects enrolled in DCCT with type 1 diabetes who were aged 18 years or older at baseline. INTERVENTION: Randomized to receive either intensive (n = 586) or conventional (n = 582) diabetes treatment with a mean follow-up of 6.1 years. MAIN OUTCOME MEASURES: Plasma lipid levels and blood pressure in each treatment group categorized by quartile of weight gain. RESULTS: With intensive treatment, subjects in the fourth quartile of weight gain had the highest body mass index (BMI) (a measure of weight adjusted for height), blood pressure, and levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B compared with the other weight gain quartiles with the greatest difference seen when compared with the first quartile (mean values for the highest and lowest quartiles: BMI, 31 vs 24 kg/m2; blood pressure, 120/77 mm Hg vs 113/73 mm Hg; triglyceride, 0.99 mmol/L vs 0.79 mmol/L [88 mg/dL vs 70 mg/dL]; LDL-C, 3.15 mmol/L vs 2.74 mmol/L [122 mg/dL vs 106 mg/dL]; and apolipoprotein B, 0.89 g/L vs 0.78 g/L; all P<.001). In addition, the fourth quartile group had a higher waist-to-hip ratio; more cholesterol in the very low density lipoprotein, intermediate dense lipoprotein, and dense LDL fractions; and lower high-density lipoprotein cholesterol and apolipoprotein A-I levels compared with the first quartile. Baseline characteristics were not different between the first and fourth quartiles of weight gain with intensive therapy except for a higher hemoglobin A1c in the fourth quartile. Weight gain with conventional therapy resulted in smaller increases in BMI, lipids, and systolic blood pressure. CONCLUSIONS: The changes in lipid levels and blood pressure that occur with excessive weight gain with intensive therapy are similar to those seen in the insulin resistance syndrome and may increase the risk of coronary artery disease in this subset of subjects with time.
Adult↗
Use of niacin, statins, and resins in patients with combined hyperlipidemia.
Patients in the original Familial Atherosclerosis Treatment Study (FATS) cohort were subgrouped into those with triglyceride levels < or = 120 mg/dL (n = 26) and those with triglyceride levels > or = 190 mg/dL (n = 40). Their therapeutic responses to niacin plus colestipol, lovastatin plus colestipol, colestipol alone, or placebo were determined. Therapeutic response was also determined in the same 2 triglyceride subgroups (n = 12 and n = 27, respectively) of patients selected for low levels of high-density lipoprotein (HDL) cholesterol and coronary artery disease. These triglyceride criteria were chosen to identify patient subgroups with high likelihood of "pattern A" (normal-size low-density lipoprotein [LDL] particles and triglyceride < or = 120 mg/dL) or "pattern B" (small dense LDL and triglyceride > or = 190 mg/dL). Our findings in these small patient subgroups are consistent with the emerging understanding that coronary artery disease patients presenting with high triglyceride levels have lower HDL-C, smaller less buoyant LDL-C, and greater very low-density lipoprotein (VLDL) cholesterol and VLDL apolipoprotein B, and are more responsive to therapy as assessed by an increase in HDL-C and reduction in triglycerides, VLDL-C, and VLDL apolipoprotein B. In the FATS high-triglyceride subgroup with these characteristics, a tendency toward greater therapeutic improvement in coronary stenosis severity was observed among those treated with either of the 2 forms of intensive cholesterol-lowering therapy. This improvement is associated with therapeutic reduction of LDL-C and elevation of HDL-C, but also appears to be associated with drug-induced improvement in LDL buoyancy.
Anticholesteremic Agents↗
Common variants in the promoter of the hepatic lipase gene are associated with lower levels of hepatic lipase activity, buoyant LDL, and higher HDL2 cholesterol.
Increased hepatic lipase (HL) activity is associated with small, dense, low density lipoprotein (LDL) and low high density lipoprotein2 (HDL2) cholesterol (-C) levels. A polymorphism in the promoter region of the HL gene (LIPC) is associated with HDL-C levels. To test whether this association is mediated by differences in HL activity between different LIPC promoter genotypes, the LIPC promoter polymorphism at position -250 (G-->A), HL activity, LDL buoyancy, and HDL-C levels were studied in white normolipidemic men and men with coronary artery disease (CAD). The less common A allele (frequency=0.21 and 0.25 in normal and CAD subjects, respectively) was associated with lower HL activity (P<0.005 by ANOVA) and buoyant LDL particles (P</=0.01) in both groups. Normal and CAD subjects heterozygous for the A allele had lower HL activity (by 24% and 29%, respectively) and significantly more buoyant LDL particles. Homozygosity for this allele (AA) was associated with an even lower HL activity in normal (-26%) and CAD (-46%) subjects. The A allele was associated with higher HDL2-C in CAD patients (P=0.007); heterozygotes and homozygotes for the A allele had a 92% and a 140% higher HDL2-C level (P<0.01) than did GG individuals. In a small number of normolipidemic subjects, the same trend in HDL2-C was seen. In a univariate analysis, the LIPC genotype accounted for 20% to 32% of the variance in HL levels among normal subjects and CAD patients, respectively. After adjustment for HL, the association between LIPC genotype and LDL buoyancy was no longer significant, suggesting that the effect of LIPC genotype on LDL buoyancy is mediated by its effects on HL activity. The LIPC A allele was more frequent in Japanese-Americans and African-Americans than in whites. In summary, these results suggest that variants in the LIPC promoter may significantly contribute to the variance in levels of HL activity and consequently, to the prevalence of the atherogenic small, dense, LDL particles and low HDL2-C levels.
Adult↗
Evidence against linkage of familial combined hyperlipidemia to the apolipoprotein AI-CIII-AIV gene complex.
Familial combined hyperlipidemia (FCHL) was originally described as a disorder characterized by elevated levels of either plasma cholesterol or triglyceride (TG) or both in members ofthe same family. More recent studies have indicated that apolipoprotein B levels (apoB) are also elevated in these individuals. Although a dominant mode of inheritance was originally proposed, recent studies have questioned this simple mode of inheritance, and the genetic basis of the disorder has eluded investigators. A study that reported evidence that FCHL is linked to the apolipoprotein AI-CIII-AIV region on chromosome 11 is therefore of interest. We have attempted to replicate this finding in three large, well-characterized FCHL kindreds by using a highly polymorphic marker in the apoCIII gene. Using the same definitions and parameters as were used in the initial report, we obtained strong evidence against linkage of FCHL to the apolipoprotein AI-CIII-AIV region on chromosome 11 (combined lod score of -7.87 at 0% recombination). Two other models, one based on total cholesterol (TC) levels alone and one based on the joint distribution of TC and apoB levels, also gave evidence against linkage of FCHL to this region (lod scores at 0% recombination of -8.95 and -2.58, respectively). An additional regression-based linkage analysis also gave no support for the existence of a locus in this region that influences these lipid levels in these pedigrees. Explanations for the differences in results between these studies include genetic heterogeneity, differences in clinical phenotype used to select the pedigrees, and ascertainment bias.
Apolipoprotein A-I↗
Detailed characterization of the binding site of the lipoprotein lipase-specific monoclonal antibody 5D2.
Monoclonal antibody (MAb) 5D2 recognizes lipoprotein lipases (LPL) from different species but not related lipases. This MAb is a unique reagent, used world-wide, because it differentiates between monomeric inactive and dimeric active LPL, inhibits human LPL enzyme activity, and binds to C-terminal LPL sequences involved in interactions with lipoproteins, lipoprotein receptors, and heparin. In this study we have analyzed the fine specificity of the MAb epitope recognition in order to better understand its functional properties and species-specific LPL immune reactivity. In peptide scan assays, MAb 5D2 reacted with all, except two, 13 amino acid-long peptides located between positions 380 and 410. Peptides from the amino terminal end of this region reacted more strongly than those from the carboxyl terminal end. Furthermore, only a peptide from the amino terminal end competed effectively with the binding of MAb 5D2 to native LPL bound to microtiter plates or nitrocellulose. A systematic peptide mutagenesis study indicated that 8 amino acids of the reactive region, mainly located in the amino terminal end, are critical for binding and probably directly interact with MAb 5D2. The experimentally determined antigenicities of species-specific LPL peptides and of the corresponding denatured full-length LPL proteins on immunoblots were consistent with these findings. According to a proposed 3D-model for LPL, only the amino terminal end of the antigenic region is easily surface-accessible. These data combined with 3D-modelling of monoclonal antibody (MAb)-lipoprotein lipase (LPL) protein interaction provide new insight into the known biological effects of MAb 5D2 on LPL and the antigenic determinants that are recognized.
Amino Acid Sequence↗
Asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia.
To further elucidate the incidence and potential mechanism of asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia (ALL), we serially obtained fasting lipid and lipoprotein studies on 38 of the 43 consecutively diagnosed children with ALL before, during, and after asparaginase therapy. We also evaluated a second population of 30 long-term survivors of childhood ALL; a fasting lipid and lipoprotein profile was obtained once at study entry. The mean peak triglyceride level during asparaginase of 465 mg/dL (standard deviation [SD] 492) was significantly higher (P = .003) than the level of 108 mg/dL (SD 46) before the initiation of asparaginase therapy. Sixty-seven percent of the newly diagnosed patients had fasting triglyceride levels greater than 200 mg/dL during asparaginase therapy; 15 patients (42%) had levels greater than 400 mg/ dL, 7 with levels greater than 1,000 mg/dL. The incidence of hypertriglyceridemia did not vary by type of asparaginase or risk status of ALL (defined by white blood cell count and age). None of the 7 patients with triglyceride levels greater than 1,000 mg/dL developed pancreatitis. In contrast, 4 of the 13 patients without triglyceride elevation developed pancreatitis; 3 of the 4 patients had fasting studies at the height of their abdominal pain. Nuclear magnetic resonance analysis of lipid subclasses showed a significant increase in the smaller, denser forms of very low density lipoprotein (VLDL) and negligible chylomicron fraction in a subset of patients with marked triglyceride elevation. Lipoprotein lipase activity was consistently above normative values for all levels of triglyceride and could not be explained by obesity or hyperglycemia. Apolipoprotein B(100) levels increased during asparaginase therapy, although the mechanism of this remains unclear. LDL reciprocally decreased with increased VLDL during asparaginase therapy. After asparaginase therapy, triglyceride levels (mean, 73 mg/dL [SD 33]) were significantly lower than levels obtained during asparaginase therapy. Triglyceride levels for survivors did not differ from the normal range or postasparaginase levels in the newly diagnosed patients. These data show a striking temporal association between asparaginase therapy and hypertriglyceridemia. Changes in cholesterol, in contrast, were not temporally related to asparaginase treatment. Cholesterol levels were elevated (>200 mg/dL) in 20% of the patients after asparaginase, which may be due to continued treatment with corticosteroids. The mean cholesterol level of long-term survivors of 177 mg/dL was significantly higher than the norm (P = .045). High-density lipoprotein (HDL) levels were significantly lower than normal at all time periods and for both populations; 25% of survivors had HDL levels less than 35 mg/dL. We conclude that modifications in asparaginase therapy are not necessary. In cases of triglyceride elevation greater than 2,000 mg/dL when the risk of pancreatitis is increased, close clinical monitoring is imperative. Larger studies are needed to determine the incidence of dyslipidemia in long-term survivors of ALL as well as the relationship between lipid abnormalities and other late effects of treatment, notably obesity and cardiomyopathies.
Adolescent↗
The central role of dietary fat, not carbohydrate, in the insulin resistance syndrome.
Compared with a diet high in total and saturated fat, a high carbohydrate diet improves insulin sensitivity and lipid levels. Recent studies have shown that subjects on an ad-lib low fat, high carbohydrate diet lose weight and, therefore, may have even greater improvement in the metabolic disturbances of the insulin resistance syndrome.
Dietary Carbohydrates↗
Regulation of body adiposity and the problem of obesity.
The hypothesis that body adiposity is homeostatically regulated is the focus of an intensive research effort, and support for this concept is rapidly growing. While generating optimism about the future of obesity treatment, these advances also bear on our current approach to the obese patient. The observation that body adiposity appears to be subject to regulation in obese as well as lean individuals suggests that common forms of obesity may result from a primary disorder of the weight-regulatory system. As a result, voluntary efforts to lower body adiposity activate compensatory responses that limit weight loss and facilitate weight regain. The use of weight-reduction strategies based on caloric restriction, therefore, effectively pits the will of the obese individual against his or her own intrinsic weight-regulatory system. Until more effective approaches to weight reduction are available, we suggest that clinical intervention should focus on patient education and strategies to limit weight gain or modestly lower weight. Since the combination of a low-fat diet with an exercise program appears to reduce the level at which body weight is regulated without active caloric restriction, this approach may be appropriate for many obese individuals.
Adipose Tissue↗
Therapeutic response to medium-chain triglycerides and omega-3 fatty acids in a patient with the familial chylomicronemia syndrome.
We have studied the underlying molecular defect in a patient presenting with recurrent pancreatitis, hypertriglyceridemia, and virtually undetectable postheparin plasma lipoprotein lipase (LPL) mass and activity, who normalized her triglycerides 3 to 6 months after initiation of either medium-chain triglyceride (MCT) oil or omega-3 fatty acid (omega-3-FA) therapy. After treatment, postheparin plasma LPL activity and mass ranged from 24% to 39% of normal and LPL specific activity was normal (1.0 nmol.ng-1.min-1). On discontinuation of MCT oil or omega-3-FA, plasma triglyceride increased to > 2000 mg/dL. Northern blotting revealed both normal size and abundance of LPL mRNA isolated from adipocytes as well as macrophages. Sequence analysis of the LPL gene, which included all 10 exons, intron-exon splice junctions, and 1.7 kb of the 5'-flanking region, and of LPL cDNA failed to identify any mutations. ApoC-II activity and mass assays revealed the presence of normal levels of a fully functional cofactor as well as the absence of circulating plasma inhibitors of lipase function. In summary, we describe a unique patient presenting with classical features of the familial chylomicronemia syndrome who manifests an unusually beneficial therapeutic response to MCT oil and omega-3-FA therapy. Unlike that in most patients with LPL deficiency, the chylomicronemia in this patient is not caused by a mutation in the structural LPL gene but possibly by a posttranscriptional defect. Thus, a subset of LPL-deficient patients with unique genetic defects respond to therapy by normalizing fasting plasma triglycerides; a therapeutic trial with MCT oil should be considered in all patients presenting with the familial chylomicronemia syndrome.
Adipose Tissue↗