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.
Humans ; Infant ; Male ; Acute Disease ; Ascites ; Cholesterol ; Hyperlipoproteinemia Type I/genetics* ; Hyperlipoproteinemias ; Lipoprotein Lipase/genetics* ; Pancreatitis ; Triglycerides

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.
Adipocytes ; Adipogenesis ; Animals ; Aspergillus ; Body Weight ; Carrier Proteins ; Diet, High-Fat ; Glycerol ; Injections, Intraperitoneal ; Intra-Abdominal Fat ; Lipase ; Lipolysis ; Lipoprotein Lipase ; Mice ; Mice, Obese ; Peroxisomes ; Rhizophoraceae ; Sterol Esterase ; Transcription Factors

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.
Abdomen ; Adipogenesis ; Blotting, Western ; Carrier Proteins ; Ectopic Gene Expression ; Humans ; In Vitro Techniques ; Lipoprotein Lipase ; Lipoproteins ; Luciferases ; Mesenchymal Stromal Cells ; Obesity ; PPAR gamma ; Real-Time Polymerase Chain Reaction ; Transcription Factors ; Transfection ; Up-Regulation

Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.
Apolipoprotein C-III ; Cardiovascular Diseases ; Diacylglycerol O-Acyltransferase ; Fatty Acids, Omega-3 ; Fibric Acids ; Hyperlipoproteinemia Type I ; Life Style ; Lipase ; Lipoprotein Lipase ; Lipoproteins ; Metabolism ; Mortality ; PPAR alpha ; Risk Factors ; Triglycerides

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.
Adipose Tissue ; Blood Glucose* ; Chronic Disease ; Dementia ; Diet ; Diet, Fat-Restricted ; Diet, High-Fat* ; Eating ; Education ; Fatty Liver ; Female ; Humans ; Hypertension ; Insulin ; Insulin Resistance ; Life Style ; Lipoprotein Lipase ; Metabolism ; Nutritionists ; Obesity ; Ovary ; Prevalence

BACKGROUND/OBJECTIVES: Elevation of postprandial lipemia characterized by a rise in triglyceride (TG)-rich lipoproteins can increase the risk of atherogenesis. The objective of this study was to investigate postprandial lipemia response to a single dietary fat/sugar load test and monitor beneficial changes induced by the consumption of Platycodi radix (AP) beverage in healthy subjects. SUBJECTS/METHODS: A total of 52 subjects were randomly assigned to either placebo or AP beverage group with a high-fat shake in a randomized controlled crossover trial. Postprandial blood was collected at 0, 1, 2, 4, and 6 h and analyzed for TG and lipoprotein lipase mass. Inhibition of pancreatic lipase was determined in vitro. RESULTS: AP inhibited pancreatic lipase activity in vitro (IC₅₀ = 5 mg/mL). Compared to placebo beverage, AP beverage consumption with a high-fat shake induced significant increase of plasma lipoprotein lipase mass (P = 0.0111, β estimate = 4.2948) with significant reduction in very low-density lipoprotein (VLDL) TG concentration (P = 0.038, β estimate = −52.69) at 6 h. Based on significant correlation between high-fat dietary scores MEDFICTS and postprandial TG responses in VLDL (P = 0.0395, r = 0.2127), subgroup analysis revealed that 6 h-postprandial VLDL TG response was significantly decreased by AP consumption in subjects with MEDFICTS ≥ 40 (P = 0.0291, β estimate = −7214). CONCLUSIONS: AP beverage might have potential to alleviate postprandial lipemia through inhibiting pancreatic lipase activity and elevating lipoprotein lipase mass. Subgroup analysis revealed that subjects with high-fat dietary pattern could be classified as responders to AP beverage among all subjects.
Atherosclerosis ; Beverages* ; Healthy Volunteers* ; Hyperlipidemias* ; In Vitro Techniques ; Lipase ; Lipoprotein Lipase ; Lipoproteins* ; Plasma ; Triglycerides

Chylomicronemia is a severe type of hypertriglyceridemia characterized by chylomicron accumulation that arises from a genetic defect in intravascular lipolysis. It requires urgent and proper management, because serious cases can be accompanied by pancreatic necrosis or persistent multiple organ failure. We present the case of a 1-month-old infant with chylomicronemia treated by plasmapheresis. His chylomicronemia was discovered incidentally when lactescent plasma was noticed during routine blood sampling during a hospital admission for fever and irritability. Laboratory investigation revealed marked triglyceridemia (>5,000 mg/dL) with high chylomicron levels. We therefore decided to perform a therapeutic plasmapheresis to prevent acute pancreatitis. Sequence analysis revealed a homozygous novel mutation in exon 4 of GPIHBP1: c.476delG (p.Gly159Alafs). Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) stabilizes the binding of chylomicrons near lipoprotein lipase and supports lipolysis. Mutations of GPIHBP1, the most recently discovered gene, can lead to severe hyperlipidemia and are known to make up only 2% of the monogenic mutations associated with chylomicronemia. The patient maintains mild hypertriglyceridemia without rebound after single plasmapheresis and maintenance fibrate medication so far. Here, we report an infant with chylomicronemia due to GPIHBP1 mutation, successfully treated by plasmapheresis.
Chylomicrons ; Exons ; Fever ; Humans ; Hyperlipidemias ; Hypertriglyceridemia ; Infant* ; Infant, Newborn* ; Lipolysis ; Lipoprotein Lipase ; Multiple Organ Failure ; Necrosis ; Pancreatitis ; Plasma ; Plasmapheresis* ; Sequence Analysis

Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix GeneChip® Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.
Acetaminophen ; Animals ; Drug-Induced Liver Injury ; Genetic Variation ; Incidence ; Lipoprotein Lipase* ; Lipoproteins* ; Liver ; Methods ; Mice ; Microarray Analysis ; Real-Time Polymerase Chain Reaction ; Receptors, GABA-A* ; Toxicogenetics ; Transcriptome

BACKGROUND/AIMS: Although lipoprotein lipase (LPL) gene Pvu II polymorphism has been associated with an increased risk of hypertriglyceridemia (HT), there is no clear consensus within the scientific community. METHODS: A meta-analysis of 1,640 subjects from six individual studies was conducted to better elucidate the potential relationship between the LPL gene Pvu II polymorphism and HT within the Chinese population. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by using fixed effect models. RESULTS: Our analysis indicated a significant association between LPL gene Pvu II polymorphism and HT within the Chinese population under allelic (OR, 1.550; 95% CI, 1.320 to 1.830; p = 1.158 × 10-7), recessive (OR, 0.540; 95% CI, 0.390 to 0.750; p = 0.0002), dominant (OR, 1.889; 95% CI, 1.501 to 2.377; p = 5.960 × 10-8), homozygous (OR, 2.167; 95% CI, 1.531 to 3.067; p = 1.242 × 10-5), heterozygous (OR, 1.810; 95% CI, 1.419 to 2.309; p = 1.842 × 10-6), and additive genetic models (OR, 1.553; 95% CI, 1.320 to 1.828; p = 1.158 × 10-7). CONCLUSIONS: Because LPL gene Pvu II restriction fragment length polymorphism polymorphism was associated with an elevated risk of HT, the P+ allele carriers of the LPL gene might be predisposed to HT.
Alleles ; Asian Continental Ancestry Group ; Consensus ; Humans ; Hypertriglyceridemia* ; Lipoprotein Lipase ; Models, Genetic ; Odds Ratio ; Polymorphism, Restriction Fragment Length

No abstract available.
Female* ; Humans ; Hyperlipoproteinemia Type I* ; Lipoprotein Lipase* ; Lipoproteins*