A case of neonatal-onset type I hyperlipoproteinemia with bloody ascites / 中国当代儿科杂志

This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the LPL gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.

New advances in nervous system of lipoprotein lipase / 中国临床药理学与治疗学

Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. LPL mainly hydrolyzes triglyceride-rich lipoproteins and provides free fatty acid (FFAs) for metabolic tissues. LPL acts as a molecular bridge between lipoproteins and cell surface lipoprotein receptors, facilitating lipoprotein uptake. Recent studies have shown that LPL is widely expressed in tissues. LPL has a variety of physiological functions, Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. LPL mainly hydrolyzes triglyceride-rich lipoproteins and provides free fatty acid (FFAs) for metabolic tissues. LPL acts as a molecular bridge between lipoproteins and cell surface lipoprotein receptors, facilitating lipoprotein uptake. Recent studies have shown that LPL is widely expressed in tissues. LPL has a variety of physiological functions, which regulates lipid metabolism and energy balance in the brain. Besides, it is closely related to Alzheimer's disease. This paper mainly reviews the latest research progress of LPL in the nervous system and provides new targets for the treatment and prevention.

Efecto de la inhibición de la proteína símil angiopoyetina tipo 3 (ANGPTL3): utilidad para el tratamiento de las dislipemias graves / Angiopoietin-like type 3 (angptl) inhibition: its role in the treatment of severe dyslipidemia

Las variantes de ANGPTL3 con pérdida de función están asociadas con efectos beneficiosos sobre el metabolismo lipídico y de carbohidratos y con riesgo reducido de enfermedad coronaria. Los cambios beneficiosos en los parámetros lipídicos que se obtienen con la inhibición de ANGPTL3 junto con la reducción en aterosclerosis que se observa en modelos animales y en estudios epidemiológicos de genética humana hacen de ANGPTL3 un nuevo objetivo terapéutico para prevenir las enfermedades cardiovasculares. Dos estrategias novedosas han surgido para inhibir esta proteína: un anticuerpo monoclonal y un oligonucleótido antisentido, con capacidad para reducir tanto el colesterol como los triglicéridos plasmáticos en forma notoria. Aunque el horizonte es promisorio, todavía no sabemos si los efectos de una variante presente desde el comienzo de la vida serán reproducidos por la inhibición de esta proteína que se realiza más tarde en la vida a través de una intervención farmacológica. (AU)

Loss-of-function ANGPTL3 variants are associated with beneficial effects on carbohydrate and lipid metabolism, and reduced risk of coronary heart disease. The beneficial changes in lipid parameters obtained by ANGPTL3 inhibition together with atheroprotection observed in animal models and in epi-demiological studies of human genetics make ANGPTL3 a new therapeutic target to prevent cardiovascular diseases. Two novel strategies have emerged to inhibit this protein: a monoclonal antibody and an antisense oligonucleotide, with the ability to significantly lower plasma cholesterol and triglycerides. Although the horizon is promising, we still do not know if the effects of a variant present from the beginning of life will be reproduced by the inhibition of this protein that takes place later in life through a pharmacological intervention. (AU)

Hipertrigliceridemia grave y síndrome de quilomicronemia familiar: una revisión de la literatura reciente / Severe hypertriglyceridemia and familial chylomicronemia syndrome: a review of recent literature

Resumen La hipertrigliceridemia (HTG) es un problema que se presenta con frecuencia en la práctica clínica. Su prevalencia en adultos es cercana al 10%. El espectro varía desde una predisposición que resulta en HTG solo en presencia de sobrepeso considerable o consumo excesivo de alcohol hasta mutaciones graves muy raras que pueden conducir a HTG grave en la infancia, incluso en ausencia de factores adicionales, como en el síndrome de quilomicronemia familiar (FCS, familial chylomicronemia syndrome). Este es un trastorno autosómico recesivo poco frecuente del metabolismo del quilomicrón que causa una importante elevación de los triglicéridos (>10 mmol/885 mg/dl). Esta condición está asociada con un riesgo significativo de pancreatitis aguda recurrente. La aproximación diagnóstica se logra mediante la caracterización fenotípica, y el hallazgo de la alteración genética ayuda a dar un diagnóstico más preciso. Además, se ha propuesto una puntuación clínica para el diagnóstico de FCS, pero necesita más validación. Las opciones de tratamiento disponibles para reducir los triglicéridos, como los fibratos y los ácidos grasos omega-3, no son eficaces en los pacientes con FCS. Actualmente, el único tratamiento sigue siendo una dieta de por vida muy baja en grasas, que reduce la formación de quilomicrones. Finalmente, los inhibidores de la apolipoproteína C-III están en desarrollo y podrían constituir opciones de tratamiento para estos pacientes. Considerando lo anterior, el objetivo de este artículo es realizar una revisión general sobre la HTG grave, con énfasis en el FCS, basados en la literatura disponible más reciente.

Abstract Hypertriglyceridemia (HTG) is a problem that occurs frequently in clinical practice. Its prevalence in adults is close to 10% and it varies between regions. The spectrum ranges from a disposition that results in HTG only in the presence of considerable overweight and/or excessive alcohol consumption to very rare serious mutations that can lead to severe HTG in childhood, even in the absence of additional factors such as familial chylomicronemia syndrome (FCS). This is a rare autosomal recessive disorder of chylomicron metabolism that causes a severe elevation in triglyceride levels (>10 mmol/885 mg/dL). This condition is associated with a significant risk of recurrent acute pancreatitis. Because this is a genetic condition, the optimal diagnostic strategy remains the genetic test. In addition, a clinical score for the diagnosis of FCS has been proposed but it needs further validation. Available treatment options to lower triglycerides, such as fibrates or omega-3 fatty acids, are not effective in patients with FCS. Currently, the cornerstone of treatment remains a very low-fat, lifetime diet that reduces chylomicron formation. Finally, apolipoprotein C-3 inhibitors are under development and may eventually be treatment options for these patients. The objective of this article is to carry out a general review of severe HTG, with an emphasis on FCS and based on the most recent available literature.

Heparin and insulin in the management of acute hypertriglyceridemic pancreatitis / Heparina e insulina en el manejo de pancreatitis aguda asociada a hipertrigliceridemia

Abstract Hypertriglyceridemic pancreatitis (HTGP) is the third cause of acute pancreatitis in most studies, with a triglyceride (TG) risk value of more than 1000 mg/dL. The pathophysiological mechanism involves triglyceride hydrolysis by pancreatic lipase and the release of fatty acids which cause damage by producing free radicals. The reduction of TGs below 500 mg/dL is the treatment goal, based on increased lipoprotein lipase activity and chylomicron degradation. We present the case of a patient with HTGP with an adequate response to concomitant insulin and heparin therapy. (Acta Med Colomb 2020; 45. DOI: https://doi.org/10.36104/amc.2020.1491).

Resumen La pancreatitis secundaria a hipertrigliceridemia (PASHT) es la tercera causa de pancreatitis aguda en la mayoría de series, teniendo como factor de riesgo un valor de triglicéridos (TG) mayor a 1000 mg/dL. El mecanismo fisiopatológico involucra la hidrólisis de triglicéridos por la lipasa pancreática y la liberación de ácidos grasos que inducen el daño por la generación de radicales libres. La reducción de los TG a niveles menores de 500 mg/dL es el objetivo del tratamiento, basado en el aumento de la actividad de la lipoproteinlipasa y degradación de quilomicrones. Presentamos un caso de un paciente que presenta PASHT con adecuada respuesta al manejo concomitante de insulina y heparina.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1491).

An Infant with Milky Serum and a Rare Mutation

A 40-day-infant having milky serum, eruptive xanthomas,hepatosplenomegaly, lipemia retinalis, high cholesterol andtriglyceride, was found to have lipoprotein lipase (LPL) deficiencyon genetic workup. Triglyceride decreased with dietary fatrestriction, medium chain triglyceride and fibrates.LPLdeficiency in early infancy can be treated with pharmacologicaland dietary interventions.

Identification of differentially expressed genes and pathways in lipoprotein lipase gene heterozygous knockout mice through gene microarray analysis / 上海交通大学学报（医学版）

Objective • To screen the differentially expressed genes (DEGs) and pathways in the islet tissues of lipoprotein lipase (Lpl) gene heterozygous knockout (Lpl+/-) mice and wild type (WT) mice, and explore the molecular mechanism of pathogenesis of type 2 diabetes mellitus (T2DM) mediated by lipotoxicity. Methods • The islets of Lpl+/- mice and WT mice were isolated and purified. DEGs were screened by gene microarray analysis. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were performed. The expressions of key genes were verified by quantitative real-time PCR (qPCR). Results • A total of 187 DEGs were identified. GO functional analysis and KEGG pathway analysis showed that DEGs were mainly involved in the biological processes such as immune cell proliferation and differentiation, inflammatory signaling pathways and cell adhesion. Among the top 10 DEGs screened from Lpl+- mice and WT mice, gremlin 1 (Grem1) gene was closely related to the function of islet β cells, while the result of qPCR was consistent with that of gene microarray analysis. Conclusion • Multiple signaling pathways are involved in the process of T2DM mediated by lipotoxicity, which may lead to the dysfunction of islet β cells by inhibiting Grem1 expression.

The beneficial effects of a water-based aerobic exercise session on the blood lipids of women with dyslipidemia are independent of their training status

OBJECTIVES: To evaluate the acute effects of a session of water-based aerobic exercise on the blood lipid levels of women with dyslipidemia and to compare these results according to their training status. METHOD: Fourteen premenopausal women with dyslipidemia, aged 40-50 years, participated in two water-based aerobic exercise sessions, the first when they were generally sedentary and the second after they were trained with a water-based aerobic training program for 12 weeks. Both experimental sessions were performed using the same protocol, lasted 45 min, and incorporated an interval method, alternating 3 min at a rating of perceived exertion (RPE) of 13 and 2 min at an RPE of 9. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and lipoprotein lipase enzyme (LPL) were obtained through venous blood collection before and immediately after each session. A generalized estimating equation method and Bonferroni tests were conducted (with time and training status as factors) for statistical analyses. RESULTS: At enrollment, the mean age of the participants was 46.57 years (95% confidence interval [CI] 44.81−48.34). The statistical analyses showed a significant time effect for all variables (TC: p=0.008; TG: p=0.012; HDL: p<0.001; LPL: p<0.001) except for LDL (p=0.307). However, the training status effect was not significant for any variable (TC: p=0.527; TG: p=0.899; HDL: p=0.938; LDL: p=0.522; LPL: p=0.737). These results indicate that the TC and TG levels reduced and the HDL and LPL concentrations increased from pre- to post-session in similar magnitudes in both sedentary and trained women. CONCLUSIONS: A single water-based aerobic exercise session is sufficient and effective to beneficially modify the lipid profile of women with dyslipidemia, regardless of their training status.

A new attempt with lipoprotein lipase agonists in the treatment of nonalcoholic steatohepatitis / 中华肝脏病杂志

Objective@#To analyze non-alcoholic steatohepatitis (NASH)-related differentially expressed genes (DEGs) by bioinformatics methods to find key pathways and potential therapeutic targets for NASH.@*Methods@#GSE61260 chip was downloaded from the public microarray database and liver biopsy samples from 24 NASH cases and 38 healthy controls were included. The Limma software package in R language was used to screen DEGs under the condition of difference multiple > 1.5 and adj. P < 0.05. The clusterProfiler software package was used for GO analysis and KEGG analysis. The STRING online database was used for protein-protein interaction analysis, and the L1000 and DrugBank databases were used for drug prediction.@*Results@#Compared with healthy control group, 857 DEGs were screened out in NASH group including 167 up-regulated genes and 690 down-regulated genes. GO analysis showed that DEGs were mainly involved in inflammation and cholesterol metabolism. KEGG analysis showed that DEGs were mainly enriched in PPAR, non-alcoholic fatty liver disease, oxidative phosphorylation and other signaling pathways. Among them, eight genes of ACSL4, CYP7A1, FABP4, FABP5, lipoprotein lipase, ME1, OLR1 and PLIN1 were enriched in PPAR signaling pathway, and 165 interaction nodes were formed with 47 DEGs-encoded proteins. Lipoprotein lipase interacted with 21 DEGs, and its up-regulated expression had improved lipid metabolism, insulin resistance and anti-inflammatory effects. Four drugs (gemfibrozil, bezafibrate, omega-3 carboxylic acid and glycyrrhizic acid) were screened by L1000 and DrugBank to activate lipoprotein lipase. Presently, these four drugs are clinically used to treat hypertriglyceridemia or to improve inflammation. In this regard, we speculated that the pharmacological effects of these four drugs had improved NASH by activating lipoprotein lipase to promote liver lipid metabolism and alleviate inflammation.@*Conclusion@#PPAR signaling pathway is closely associated to the occurrence and development of NASH, and thereby lipoprotein lipase agonist is a new attempt to treat NASH.

Research progress of lipoprotein lipase gene mutation in patients with hypertriglyceridemia / 中华检验医学杂志

Hypertriglyceridemia is a syndrome characterized by abnormal triglyceride synthesis or degradation. High triglycerides is an independent risk factor for cardiovascular disease. Some study found that in addition to lifestyle, such as nutrition and their own activities, the genetic factors also determine the concentration of plasma triglycerides. Lipoprotein lipase is a rate-limiting enzyme for triglyceride degradation, which plays an important role in lipid metabolism, insulin resistance, and adipocyte differentiation. In recent years, family analysis and genome-wide association analysis (GWAS) have identified genes associated with hypertriglyceridemia, including the LPL gene, which mutates to reduce lipoprotein esterase activity and affect its protein content, resulting in hypertriglyceridemia. This paper reviewed the LPL gene structure, function, expression regulation, commonly used detection method and the relationship between LPL gene mutation and hypertriglyceridemia.

MicroRNA-138 Suppresses Adipogenic Differentiation in Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting Lipoprotein Lipase

PURPOSE: Adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (AMSCs) is critical to many disease-related disorders, such as obesity and diabetes. Studies have demonstrated that miRNA-138 (miR-138) is closely involved in adipogenesis. However, the mechanisms affected by miR-138 remain unclear. This work aimed to investigate interactions between miR-138 and lipoprotein lipase (LPL), a key lipogenic enzyme, in AMSCs. MATERIALS AND METHODS: Human AMSCs (hAMSCs) isolated from human abdomen tissue were subjected to adipogenic differentiation medium. Quantitative real-time polymerase chain reaction and Western blot assay were applied to measure the expressions of miR-138, LPL, and the two adipogenic transcription factors cytidine-cytidine-adenosine-adenosine-thymidine enhancer binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ). The relationship between miR-138 and LPL was predicted utilizing the miRTarBase database and validated by dual luciferase reporter assay. RESULTS: Showing increases in C/EBPα and PPARγ expression levels, hAMSCs were induced into adipogenic differentiation. During adipogenesis of hAMSCs, miR-138 expression was significantly downregulated. Overexpression of miR-138 by transfection inhibited hAMSCs adipogenic differentiation in vitro. Mechanically, LPL was a target of miR-138. LPL expression was upregulated during adipogenesis of hAMSCs, and this upregulation was reversed by miR-138 overexpression. Functionally, silencing of LPL by transfection exerted similar inhibition of the expressions of C/EBPα and PPARγ. Meanwhile, LPL ectopic expression was able to partly abolish the suppressive effect of miR-138 overexpression on adipogenic differentiation of hAMSCs. CONCLUSION: Upregulation of miR-138 inhibits adipogenic differentiation of hAMSCs by directly downregulating LPL.

Autoantibodies and hypertriglyceridemia / 中华临床营养杂志

Autoantibodies are related to occurrence of some types of severe hypertriglyceridemia. Resear-ches showed that autoantibodies of lipoprotein lipase, glycosylphosphatidylinositol-anchored high-density lipo-protein binding protein 1 and apolipoprotein C-Ⅱcould induce hypertriglyceridemia. This review focused on hy-pertriglyceridemia induced by autoantibodies and its treatment.

Impact of 1 25(OH) 2 D 3 on TG content in liver of rats with type 2 diabetes

Abstract Purpose: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. Methods: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. Results: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P <0.05), while the TG content was significantly lower than that in T2DM group (P <0.05). Conclusion: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.

Evaluation of progression and curative effect of retinoblastoma patients by detecting LPL and mRNA in CSF / 中华检验医学杂志

Objective@#To evaluate the levels of 1ipoprotein lipase protein (LPL)and mRNA in cerebrospinal fluid (CSF) for children retinoblastoma(RB)and evaluation of the chemotherapy.@*Methods@#Case-control study. Total 36 cases were collected in Beijing Tongren Hospital From October 2015 to May 2017. There were two groups, 19 cases of central nervous system(CNS) metastasis and 17 cases of non CNS metastasis according to laterality, age and gender. The changes of neuronspecific enolase (NSE) in serum and cerebrospinal fluid (CSF), chloride, glucose and quantitative protein and white blood cell count in CSF were compared between the two groups before initiating chemotherapy and after the third and sixth cycles of chemotherapy. LPL expression was assessed by Western blot and RT-PCR.Comparisonsbetweenthetwo groups of general data were performed usingt-test. The measurement data were expressed by mean ± standard deviation, and variance analysis was conducted.@*Results@#The level of CSF-NSE from CNS metastasis group was significantly higher than non CNS metastasis group(F=16.43, P=0.002). The level of serum NSE from CNS metastasis group was significantly higher than non CNS metastasis group before chemotherapy(F=41.06, P=0.006). There were significant differences in the level of serum NSE in CNS metastasis group before and after chemotherapy (F=7.06, P=0.001). CSF-LPL protein expression in the CNS metastasis group was significantly higher than that of non CNS metastasis group (F=2.57, P=0.001). There were significant differences of LPL expression in CNS metastasis group before and after chemotherapy (F=2.63, P=0.003)).@*Conclusion@#The expression of LPL protein in CNS may be related to the progression and chemotherapyof RB with CNS metastasis. (Chin J Lab Med, 2018, 41: 608-614)

Association of HindⅢ polymorphism in the lipoprotein lipase gene with diabetes mellitus :an updated Meta-analysis / 国际检验医学杂志

Objective An updated Meta-analysis was undertaken to evaluate the recent progress in the as-sociation of lipoprotein lipase (LPL) gene HindⅢ polymorphism with diabetes mellitus (DM).Methods Da-tabases including PubMed ,OvidSP ,Web of Science ,CBM ,CNKI and Wanfang were systemically searched to collect all case-control studies on the correlation between LPL HindⅢ polymorphism and DM.According to the selection criteria ,2 reviewers independently screened the literatures ,extracted data and evaluated the quali-ty of the included studies.Meta-analysis was completed by using Stata 14.0 software.Results 21 groups of data from 20 literatures were included with 2 634 DM patients and 3 375 controls.The results of meta-analysis showed that the frequencies of G allele (OR=0.83 ,95% CI :0.69 -0.99 ,P=0.04) and the dominant model [(TG+GG) vs.TT :OR=0.79 ,95% CI :0.63-0.99 ,P=0.04] in DM patients were associated with the re-duction in the risk of DM.Compared with TT genotype ,plasma triglyceride levels were obviously reduced in DM patients with TG +GG genotype and GG genotype.Furthermore ,total cholesterol levels in DM patients with TG+GG genotype were markedly decreased ,while HDL-C levels were significantly increased in DM pa-tients with TG+ GG genotype.Conclusion The G allele and TG + GG genotype of LPL HindⅢ polymor-phism may be protective factors for DM ,which can reduce the risk of DM by ameliorating the abnormalities of lipid metabolism.However ,large-scale and high-quality clinical trials on the association between LPL HindⅢ polymorphism and DM are still needed for further clarification.

Blood Sugar Control and Low-Carbohydrate High-Fat Diet / 임상당뇨병

Diabetes patients and pre-diabetic patients are increasing worldwide. Type 2 diabetes starts with insulin resistance, and the long-term habit of stimulating insulin secretions causes insulin resistance and accumulates body fat to develop obesity and non-alcoholic fatty liver into diabetes. It also causes a variety of chronic diseases such as high blood pressure, polycystic ovary diseases, cancer and dementia. Insulin resistance is caused by an unbalanced lifestyle, and among other factors, the balance of the macronutrient is a very important factor. Koreans are characterized by high carbohydrate intake. Given the increasing prevalence of diabetes and the characteristics of Korean physical and eating habits, a more effective balance of diet education is needed. Therefore, it is very important for clinical dietitian to understand the carbohydrate and fat metabolism caused by insulin, and the concept of balanced diet for blood sugar control needs to be shifted from low-fat high-carbohydrate diet to low-carbohydrate high-fat diet.

Fenofibrate ameliorates insulin resistance in lipoprotein lipase heterozygous knockout mice and its possible mechanisms / 中华内分泌代谢杂志

Objective To investigate the effect of fenofibrate on glucolipid metabolism and insulin sensitivity in lipoprotein lipase heterozygous knockout ( LPL+/-) mice, and to explore its mechanism. Methods LPL+/- mice and wild type ( WT) C57 mice were selected and divided into 3 groups ( n=6 each group):LPL+/-( FB) group, LPL+/-(W)group,andWTgroup.MiceinLPL+/-(FB)groupweregavagedwithfenofibrate(50mg·kg-1·d-1)for8 weeks. Mice in LPL+/-( W) and WT groups were orally fed with the same volume water as that in LPL+/-( FB) group for 8 weeks. Body weight was observed. Plasma triglyceride ( TG ) and free fatty acid ( FFA ) were measured. Intraperitoneal glucose tolerance test in 3 groups of mice were performed. The glucose area under the curve ( AUCG) and homeostasis model assessment for insulin resistance index ( HOMA-IR) were calculated. Insulin-stimulated Ser473 Akt phosphorylation in liver and skeletal muscle was measured by Western blot. Reactive oxygen species ( ROS) levels in liver and skeletal muscle were determined by dihydroethidium staining method and superoxide dismutase ( SOD) and catalase ( CAT) mRNA expression levels were detected by real-time PCR. Results Compared with LPL+/-( W) mice, body weight of LPL+/-( FB) mice was lowered, plasma TG and FFA levels were decreased by about 46.0％and 76.5％respectively, and fasting insulin level and HOMA-IR were decreased while there were no significant differences in fasting glucose level and AUCG between two groups. Insulin-stimulated Ser473 Akt phosphorylation levels in liver and skeletal muscle of LPL+/-mice were enhanced by fenofibrate. ROS level in skeletal muscle of LPL+/-( FB) mice was lower than that in LPL+/-( W) mice while there was no significant difference in ROS of liver between two groups. Fenofibrate significantly increased SOD and CAT mRNA expressions in skeletal muscle of LPL+/-mice, but not in liver. Conclusion Fenofibrate reduces body weight, ameliorates lipid metabolism, and improves insulin sensitivity in LPL+/- mice, with reduced oxidative stress.

Molecular mechanism of familial hypertriglyceridemia caused by lipoprotein lipase gene mutation (C310R/E396V) / 中华内分泌代谢杂志

Objective The purpose of this study is to investigate the molecular mechanisms of p.C310R(c.T928C) and p.E396V(c.A1187T) lipoprotein lipase(LPL) gene mutations in vitro, which may help to construct the spectrum of LPL gene mutations and phenotype. It also can provide accurate early diagnosis for high-risk population of familial hypertriglyceridemia and provide the basis for the development of gene targeted therapy. Methods Genomic DNA was extracted from proband′s family members′ peripheral blood cells and screened by whole-exome sequencing to verify candidate gene variations. PCR products were afterwards directly sequenced again to confirm corresponding LPL variants. At the cellular level, lentiviruses containing LPL mutations were constructed and then transfected into COS-1 cells. Functional significance of the mutants was corroborated by analyzing LPL activity and mass in the cell medium and lysates via ELISA and enzyme-fluorescent method. mRNA was assayed by RT-PCR to confirm the effect on gene transcription. Results DNA sequence analysis revealed that the proband was a heterozygote for a novel c.T928C mutation in exon 6 of LPL gene, while his nephew was a compound heterozygote for the c.T928C mutation in exon 6 and a novel c.A1187T mutation in exon 8. In vitro studies, these two mutations can cause decreased activity and mass of extracellular LPL(P<0.05). Moreover, further investigation indicated that LPL C310R mutation tremendously affected post-transcriptional modification of LPL gene, whereas LPL E396V mutation dampened intracellular LPL trafficking. Conclusion Both the mutations are pathogenic by reducing the activity and mass of LPL in the plasma, which affected normal metabolism of triglycerides.

Lipoprotein lipase gene polymorphisms and atherosclerosis / 国际脑血管病杂志

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of the triglyceride core of circulating triglyceride-rich lipoproteins.LPL can not only affect the lipoprotein level,but also play an important role in the development of atherosclerosis.LPL gene polymorphisms may affect LPL activity,and therefore have both pro-and anti-atherogenic effects.This article reviews the relationship between LPL gene polymorphism and atherosclerosis.

Role of RNA-binding protein HuR in human adipocyte differentiation / 中华内分泌代谢杂志

Objective To investigate the expressions of RNA-binding protein human antigen R(HuR), fatty acid binding protein type 4(FABP4),fatty acid synthetase(FASN),and lipoprotein lipase(LPL)during the differentiation of human adipocytes, and to explore their possible roles. Methods Human adipose-derived mesenchymal stem cells were induced by adipogenic differentiation,and the adipogenesis of cells was observed by oil red O staining. The expressions of HuR,FABP4,FASN,and LPL mRNA and protein were detected by real-time PCR and Western blotting. After HuR was silenced by siRNA, the change of adipogenesis for human adipose-derived mesenchymal stem cells was observed and the expressions of adipogenic genes were detected. Results The expressions of HuR,FABP4,FASN,and LPL mRNA and protein were significantly increased after human adipose-derived mesenchymal stem cells were induced to differentiate into adipocytes(all P<0.01). After HuR expression was down-regulated by siRNA,the adipogenic level of human adipose-derived mesenchymal stem cells was reduced,with decreased protein levels of FABP4,FASN,and LPL(all P<0.05),which were without changes for their mRNA levels. Conclusion HuR promotes the differentiation of human adipocytes mainly via regulating the changes of FABP4,FASN,and LPL protein levels.