Lipoprotein Lipase Levels Research Articles

Integrin β3 Deficiency Results in Hypertriglyceridemia via Disrupting LPL (Lipoprotein Lipase) Secretion.

Integrin β3 is implicated in numerous biological processes such as its relevance to blood triglyceride, yet whether β3 deficiency affects this metabolic process remains unknown. Approach and Results: We showed that the Chinese patients with β3-deficient Glanzmann thrombasthenia had a 2-fold higher serum triglyceride level together with a lower serum LPL (lipoprotein lipase) level than those with an αIIb deficiency or healthy subjects. The β3 knockout mice recapitulated these phenotypic features. The elevated plasma triglyceride level was due to impaired LPL-mediated triglyceride clearance caused by a disrupted LPL secretion. Further analysis revealed that β3 directly bound LPL via a juxtamembrane TIH (threonine isoleucine histidine)720-722 motif in its cytoplasmic domain and functioned as an adaptor protein by interacting with LPL and PKD (protein kinase D) to form the PKD/β3/LPL complex that is required for β3-mediated LPL secretion. Furthermore, the impaired triglyceride clearance in β3 knockout mice could be corrected by adeno-associated virus serotype 9 (AAV9)-mediated delivery of wild-type but not TIH720-722-mutated β3 genes. This study reveals a hypertriglyceridemia in both β3-deficient Chinese patients and mice and provides novel insights into the molecular mechanisms of the significant roles of β3 in LPL secretion and triglyceride metabolism, drawing attention to the metabolic consequences in patients with β3-deficient Glanzmann thrombasthenia.

Lipoprotein lipase levels in patients with Coronary Artery Disease with Type 2 Diabetes Mellitus

Lipoprotein lipase levels in patients with Coronary Artery Disease with Type 2 Diabetes Mellitus

Intermittent chylomicronemia caused by intermittent GPIHBP1 autoantibodies

Chylomicronemia caused by a deficiency in lipoprotein lipase (LPL) or GPIHBP1 (the endothelial cell protein that transports LPL to the capillary lumen) is typically diagnosed during childhood and represents a serious, lifelong medical problem. Affected patients have high plasma triglyceride levels (>1500 mg/dL) and a high risk of acute pancreatitis. However, chylomicronemia frequently presents later in life in the absence of an obvious monogenic cause. In these cases, the etiology for the chylomicronemia is presumed to be “multifactorial” (involving diabetes, drugs, alcohol, or polygenic factors), but on a practical level, the underlying cause generally remains a mystery. Here, we describe a 15-year-old female with chylomicronemia caused by GPIHBP1 autoantibodies (which abolish LPL transport to the capillary lumen). Remarkably, chylomicronemia in this patient was intermittent, interspersed between periods when the plasma triglyceride levels were normal. GPIHBP1 autoantibodies were easily detectable during episodes of chylomicronemia but were undetectable during periods of normotriglyceridemia. During the episodes of chylomicronemia (when GPIHBP1 autoantibodies were present), plasma LPL levels were low, consistent with impaired LPL transport into capillaries. During periods of normotriglyceridemia, when GPIHBP1 autoantibodies were absent, plasma LPL levels normalized. Because the chylomicronemia in this patient was accompanied by debilitating episodes of acute pancreatitis, the patient was ultimately treated with immunosuppressive drugs, which resulted in disappearance of GPIHBP1 autoantibodies and normalization of plasma triglyceride levels. GPIHBP1 autoantibodies need to be considered in patients who present with unexplained acquired cases of chylomicronemia.

Verification and Analysis of Sheep Tail Type-Associated PDGF-D Gene Polymorphisms.

Simple SummaryPDGF-D can be considered a candidate gene for selection for sheep tail type. This study investigated genetic variation of the PDGF-D gene in sheep with different tail types verified at a cellular level and revealed the molecular mechanism of PDGF-D in sheep tail fat deposition. We detected a total of two SNPs among 533 sheep. g.4122606 C > G site was significantly correlated with tail length, and g.3852134 C > T site was significantly correlated with tail width. In addition, overexpression of PDGF-D in sheep preadipocytes can promote adipogenic differentiation. The PDGF-D gene may participate in sheep tail fat deposition and could be used for molecular marker-assisted selection of sheep tail type.The aim of this study was to examine the correlation between the platelet-derived growth factor-D (PDGF-D) gene and sheep tail type character and explore the potential underlying mechanism. A total of 533 sheep were included in this study. Polymorphic sites were examined by Pool-seq, and individual genotype identification and correlation analysis between tail type data were conducted using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF-MS) method. JASPART website was used to predict transcription factor binding sites in the promoter region with and without PDGF-D gene mutation. The effect of PDGF-D on adipogenic differentiation of sheep preadipocytes was investigated. Two single nucleotide polymorphism sites were identified: g.4122606 C > G site was significantly correlated with tail length, and g.3852134 C > T site was significantly correlated with tail width. g.3852134 C > T was located in the promoter region. Six transcription factor binding sites were eliminated after promoter mutation, and three new transcription factor binding sites appeared. Expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoproteinlipase (LPL) were significantly up-regulated upon PDGF-D overexpression. Oil red O staining showed increased small and large oil drops in the PDGF-D overexpression group. Together these results indicate the PDGF-D gene is an important gene controlling sheep tail shape and regulating sheep tail fat deposition to a certain degree.

EXPRESSION OF LIPOPROTEIN LIPASE AND c-MYC ONCOGENE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AFFECTED BY THE CHORNOBYL ACCIDENT.

to determine the association between the expression of lipoprotein lipase (LPL) and c-MYC genes inperipheral blood cells of chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophedepending on the mutational status of IGHV genes. Analysis was performed in the group of 69 CLL patients irradiated due to the Chornobyl NPP accident (58clean-up workers of 1986 year, 6 inhabitants of radionuclide contaminated areas, and 5 evacuees). The IGHV genemutational status was studied by polymerase chain reaction (PCR) followed by direct sequencing. LPL and c-MYCexpression was evaluated by Quantitative Real-time PCR. Data were analyzed with the SPSS software package, version 20.0. Relative LPL expression levels in CLL samples ranged from 0 to 1663.5 (mean 138.47 ± 30.69, median 26.1).A strong correlation between individual LPL expression levels and IGHV mutational status was found (r = 0.684;p < 0.0001). The average relative c-MYC expression level was 5.7 ± 0.87 (median 2.86; range 0-48.5). No association between c-MYC expression and IGHV mutational status was found. Among unmutated IGHV cases, a correlationbetween LPL and c-MYC gene expression levels was identified: r = 0.351; p = 0.013. Our data confirm the dominant concept that unmutated IGHV CLL cases are more sensitive to the actionof proliferative stimuli compared to mutated IGHV CLL cases. This is manifested by an increase in the expression ofa functionally significant LPL gene, is one for the strongest negative prognostic markers in CLL.

Postnatal Expressional Patterns of Adipose-Associated Molecules in the Mouse Proximal Epididymal Fat.

The epididymal fat pad is a male gonadal adipocyte tissue and is histochemically separated into distal and proximal parts. The development of epididymal fat during postnatal period has not been examined in detail. A previous research showed that expression of adipocyte-associated molecules in the distal epididymal fat of mouse is generally increased as postnatally aged. In the present study, expressional patterns of same adipocyte-associated molecules in the mouse proximal epididymal fat at 2, 5, 8, and 12 months of age were studied by quantitative real-time PCR analysis and were compared with those in the distal epididymal fat. The expressional levels of peroxisome proliferator-activated receptor gamma (Pparg), lipoprotein lipase (Lpl), and fatty acid synthase (Fasn) at 5 months of age were significantly lower than those at 2 months of age, while transcript level of leptin (Lep) at 5 months was higher than that at 2 months of age. The transcript levels of all molecules at 8 months of age were significantly increased, compared with those at 2 and 5 months of age. At 12 months of age, expression of delta like non-canonical Notch ligand 1 (Dlk1) was further significantly increased, while there was no change on the transcript level of Pparg and significant decreases of Fabp4, Retn, Lpl, Lep, Fasn, and adiponectin (Adipoq) transcript levels. The current findings show that expressional patterns of molecules associated with adipocyte in the proximal epididymal fat is somewhat different with those of the distal epididymal fat, suggesting the existence of regional variance in the epididymal fat.

Orlistat increases arsenite tolerance in THP-1 derived macrophages through the up-regulation of ABCA1

Orlistat is an FDA-approved over-the-counter drug to treat obesity through the inhibition of lipase activity. Macrophages, which express high levels of lipoprotein lipase (LPL), are important phagocytes in the innate immune system. Our previous studies indicated that environmentally relevant concentrations of arsenite (As+3) could inhibit the major immune functions of macrophages. As the down-regulation of LPL is known to increase the expression of ABCA1, the cholesterol exporter demonstrated to be related to the resistance of arsenic toxicity. We examined if orlistat could reverse the inhibitive effects of As+3 on macrophage functions. The results showed that 50 μM orlistat reversed As+3-induced suppressions on phagocytosis, NO production and cytokine secretion in THP-1 derived macrophages. The expression of ABCA1 was significantly increased by orlistat in As+3 co-treated macrophages, which was associated with decreased intracellular As+3 levels. Collectively, these results indicated that orlistat could reverse the suppressive effects induced by As+3 in macrophages through the increased expression of ABCA1, which has the potential to be developed as a therapeutic agent for arsenic-induced immunosuppression.

Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats.

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are hormones secreted from the enteroendocrine cells after a meal. They exert their actions through activation of G protein-coupled receptors (R), the GIPR and GLP-2R, respectively. Both have been reported to influence metabolism. The purpose of the study was to investigate the role of the hormones in the regulation of lipid and bone homeostasis by subchronic treatment with novel GIPR and GLP-2R antagonists. Rats were injected once daily with vehicle, GIPR, or GLP-2R antagonists for 3 weeks. Body weight, food intake, body composition, plasma lipoprotein lipase (LPL), adipokines, triglycerides and the marker of bone resorption carboxy-terminal collagen crosslinks (CTX), were examined. In rats, subchronic treatment with GIPR antagonist, rat GIP (3-30)NH2, did not modify food intake and bone resorption, but significantly increased body weight, body fat mass, triglycerides, LPL, and leptin levels compared with vehicle treated rats. Subchronic (Pro3)GIP (a partial GIPR agonist), GLP-2(11-33), and GLP-2(3-33) (GLP-2R antagonists) treatment did not affect any parameter. The present results would be consistent with a role for GIP, but not GLP-2, in the maintenance of lipid homeostasis in rats, while neither GIPR nor GLP-2R antagonism appeared to influence bone resorption in rats.

Anti-Obesity Effects of Lactobacillus fermentum CQPC05 Isolated from Sichuan Pickle in High-Fat Diet-Induced Obese Mice through PPAR-α Signaling Pathway.

Sichuan pickle is a traditional fermented food in China which is produced by the spontaneous fermentation of Chinese cabbage. In this study, the anti-obesity effects of a new lactic acid bacterium (Lactobacillus fermentum CQPC05, LF-CQPC05) isolated from Sichuan pickles were assessed in vivo. An obese animal model was established in mice by inducing obesity with high-fat diet. Both serum and tissues were collected from the mice, and then subjected to qPCR and Western blot analyses. The results showed that LF-CQPC05 could decrease the values of hepatosomatic, epididymal fat, and perirenal fat indices that were induced by a high-fat diet in mice. Moreover, LF-CQPC05 reduced the levels of alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), and increased the level of high-density lipoprotein cholesterol (HDL-C) in both serum samples and liver tissues of obese mice fed with a high-fat diet. Pathological observations demonstrated that LF-CQPC05 could alleviate the obesity-induced pathological changes in the liver tissue of mice, and reduce the degree of adipocyte enlargement. The results of qPCR and Western blot analyses further indicated that LF-CQPC05 upregulated the mRNA and protein expression levels of lipoprotein lipase (LPL), PPAR-α: peroxisome proliferator-activated receptor-alpha (PPAR-α), (cholesterol 7 alpha-hydroxylase) CYP7A1, and carnitine palmitoyltransferase 1 (CPT1A), and downregulated the expression levels of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and CCAAT enhancer-binding protein alpha (C/EBP-α) in both liver tissue and epididymal adipose tissue. Taken altogether, this study reveals that LF-CQPC05 can effectively inhibit high-fat diet-induced obesity. Its anti-obesity effect is comparable to that of l-carnitine, and is superior to that of Lactobacillus delbrueckii subsp. bulgaricus, a common strain used in the dairy industry. Therefore, LF-CQPC05 is a high-quality microbial strain with probiotic potential.

Daming capsule, a hypolipidaemic drug, lowers blood lipids by activating the AMPK signalling pathway

Background/aimsHyperlipidaemia is a major risk factor for cardiovascular and cerebrovascular diseases. Daming capsule (DMC), a medicine for lowering blood lipids, is marketed in China; however, its mechanism is unclear. The present study aimed to investigate the mechanism by which DMC reduces blood lipids. Methods and resultsA rat model of hyperlipidaemia was established by feeding rats a high-fat diet (HFD), and the serum lipid levels were detected with an automatic biochemical analyser. DMC (162 mg/kg) and atorvastatin calcium (10 mg/kg) were orally administered to the hyperlipidaemic rats for 4 weeks. HFD feeding markedly induced increases in the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c); however, DMC treatment significantly decreased the levels of TC, TG, and LDL-c in rats serum. Meanwhile, the hepatic TC and TG levels, liver weight/body weight ratio, and body weight were significantly lower in the DMC-treated rats than in the HFD rats. Moreover, DMC significantly alleviated hepatomegaly, hepatic lipid deposition, and hepatic steatosis. The protein expression level of phospho-adenosine monophosphate-activated protein kinase (p-AMPK) (Thr172) in HFD rat livers was lower than that in normal rat livers, whereas it increased in the liver of the DMC-treated rats; however, the protein expression level of total-AMPK in the liver was not different among the groups. The AMPK-activating effect of DMC was blocked by Compound C (a specific AMPK inhibitor) in HepG2 cells. Additionally, DMC considerably increased peroxisome proliferator-activated receptor-alpha (PPARα) protein expression and lipoprotein lipase (LPL) transcription and concentration in the liver. This effect of DMC was also inhibited by Compound C in HepG2 cells. DMC also promoted LDL receptor (LDLR) protein expression by activating AMPK. We further found that DMC reduced the levels of TC and TG in oleic acid-treated HepG2 cells, and it restored the expression levels of p-AMPK, PPARα, LPL, and LDLR compared to the decreased levels observed in oleic acid-treated HepG2 cells. ConclusionDMC lowered lipids in serum and the liver by activating AMPK. On the one hand, the activation of AMPK enhanced PPARα expression and LPL transcription to lead to the hydrolysis of TG; on the other hand, it increased LDLR protein expression to promote lipid metabolism.

Antidiabetic and Hypolipidemic Effects of a Novel Dual Peroxisome Proliferator-Activated Receptor (PPAR) α/γ Agonist, E3030, in db/db Mice and Beagle Dogs

We investigated the antidiabetic effects of E3030, which is a potent dual activator of peroxisome proliferator-activated receptor (PPAR) α and PPARγ, in an animal model of diabetes, C57BL/KsJ-db/db mice (db/db mice), and the lipidemic effects of E3030 in beagle dogs, whose PPARα and PPARγ transactivation responses to E3030 were similar to those of humans. E3030 activated human PPARα, mouse PPARα, dog PPARα, human PPARγ, mouse PPARγ, and dog PPARγ with EC50 values of 65, 920, 87, 34, 73, and 34 nM, respectively, in the chimeric GAL4-PPAR receptor transactivation reporter assay. In db/db mice orally administered E3030 decreased blood glucose, triglyceride (TG), non-esterified fatty acids (NEFA), and insulin levels and increased blood adiponectin levels during a 14-day experimental period. Significant effects on blood glucose and adiponectin levels were observed at a dose of 3 mg/kg or greater. Furthermore, significant effects on blood TG, NEFA, and insulin levels were observed at doses of 1 mg/kg or more. An oral glucose tolerance test (OGTT) performed on Day 15 showed that E3030 at 3 mg/kg improved glucose tolerance in this model. Fourteen days of oral treatment with E3030 at a dose of 0.03 mg/kg or greater showed remarkable TG- and non high-density lipoprotein (non-HDL) cholesterol–lowering effects in beagle dogs. These results were similar to those observed for the PPARα agonist fenofibrate. E3030 also reduced apo C-III levels on Days 7 and 14, and elevated lipoprotein lipase (LPL) levels on Day 15. These results indicate that the TG- and non-HDL cholesterol-lowering actions of E3030 involve combined effects on reduction of apo C-III and elevation of LPL, resulting in increased lipolysis. The experimental results in animals suggest that E3030 has potential for use in the treatment of various aspects of metabolic dysfunction in type 2 diabetes, including dyslipidemia, hyperglycemia, hyperinsulinemia, and impaired glucose disposal.

Effects of replacing fish meal with rendered animal protein blend on growth performance, hepatic steatosis and immune status in hybrid grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂)

An 8-week growth trial was conducted to evaluate the effects of substitution of fish meal (FM) by rendered animal protein blend (APB) consisting of poultry by-product meal (PBM), shrimp meal (SM) and spray-dried blood meal (BM) in diets of juvenile hybrid grouper, Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂ (32.51 ± 0.31 g). A basal diet (FM70) with FM as the sole protein source was compared to diets progressively replacing 20% (FM56), 40% (FM42), 60% (FM28) and 80% (FM14) of FM protein. No significant differences were found in final body weight (FBW) and weight gain (WG) of fish when up to 80% of FM protein was replaced by APB. The feed efficiency (FE) and protein efficiency ratio (PER) were markedly decreased when dietary APB inclusion levels exceeded 40%. The heaptosomatic index (HSI) and whole body crude lipid content increased as dietary APB levels increased. Plasma cholesterol (CHO), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDL-C) contents of fish fed the APB containing diets were higher than the control group. Liver histological analysis showed the amounts of hepatic vacuoles and lipid droplets were significantly increased as dietary APB levels increased, which is a sign of hepatic steatosis. Moreover, dietary APB inclusion up-regulated the mRNA levels of lipid metabolism-related genes including peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmitoyltransferase 1 (CPT1), fatty acid synthase (FAS) and apolipoprotein AI (Apo-AI) while down-regulated lipoprotein lipase (LPL) levels. On the other hand, dietary APB inclusion also up-regulated the apoptosis-related genes including caspase-3, caspase-8, caspase-9 and p53 as well as inflammation-related genes including interleukin 8 (IL-8), interleukin 10 (IL-10) and transforming growth factor β1 (TGF-β1) in the liver of hybrid grouper. In conclusion, up to 80% FM can be replaced by APB protein in diets for hybrid grouper juveniles without compromising growth performance, and high levels of dietary APB could induce hepatic steatosis and thus impair the immune status of hybrid grouper.

Can Inflammatory and Nutritional Serum Markers Predict Chemotherapy Outcomes and Survival in Advanced Stage Nonsmall Cell Lung Cancer Patients?

Purpose. To determine the values of prognostic nutritional and inflammatory markers in chemotherapy outcomes and survival in the patients with advanced nonsmall cell lung cancer (NSCLC) and also in the secondary malnutrition and cachexia. Methods. Twenty-five patients with diagnosis of aNSCLC were registered for the prospective study. Malnutrition was determined by the Subjective Global Assessment (SGA) and performance status by criteria of the Eastern Cooperative Oncology Group (ECOG). Before treatment, serum levels of albumin, prealbumin, vitamin D, zinc (Zn), C-reactive protein (CRP), IL-6, IL-1 β, TNF-α, lipoprotein lipase (LPL), and the Glasgow Prognostic Score (GPS) were recorded. Patients were followed prospectively for treatment outcomes and survival. Results. Due to the deaths of 18 patients during the 4-month follow-up period, no adequate measurements of inflammatory and nutritional markers could be performed. However, seven patients completed the treatment period and evaluations of these markers could be performed during the three periods. Eighty-four percent of patients were male with a mean age of 63.3 ± 8.7 years. Evaluation of the malnutrition by SGA showed that 5 (20%) patients were well nourished (A), 12(48%) were moderately malnourished (B), and 8(32%) were severely malnourished (C). Low levels of serum albumin (<3.5g/dl), prealbumin (<20 mg/ml), 25-hydroxycholecalciferol (<30 ng/ml), and Zn (<70mg/ml) were detected in 15(60%), 17(68%), 24 (96%), and 22 (88%) patients, respectively. Elevated levels of CRP (≥10 mg/L), IL6 (≥18pg/ml), TNF-α (≥24pg/ml), IL-1β (≥10pg/ml), and LPL (<12pg/ml) were found in 24 (96%), 11(44%), 9(36), 13(52%), and 11(44%) patients, respectively. Moderate and severe malnutrition, acute phase response, and reduced survival were determined in patients with NCSLC. In 7 patients that completed the treatment period, there was an association between elevated serum levels of IL-6, IL-1β, TNF-α, CRP, and LPL and also the reduced serum levels of albumin, prealbumin, Zn, vitamin D, and GPS, respectively. Similarly, Friedman analysis indicated that prealbumin significantly increased (p=0.007) in the follow-up period. But the serum levels of CRP (mean 37.3±22.3; Wilcoxon test P=0.368) in the seven patients were lower than those of the 18 patients that expired (mean 75.82±56.2). Conclusion. Malnutrition and cachexia negatively influence oncological outcomes in patients with NSCLC. These nutritional/inflammatory markers may be useful for selection of high risk and reduced survival in patients with aNSCLC undergoing adjuvant chemotherapy.

Impact of serum levels of lipoprotein lipase, hepatic lipase, and endothelial lipase on the progression of coronary artery disease

PurposeThe purpose of this study was to investigate the relationship between serum levels of lipoprotein lipase (LPL), hepatic lipase (HL), and endothelial lipase (EL) and the progression of coronary artery disease (CAD). Materials and methodsAccording to the inclusion criteria, exclusion criteria, diagnostic criteria, angiography results, and the random matching scheme, the enrolled patients were divided into the following two groups: the progression-free group (n = 47) and the progression group (n = 15). The baseline characteristics and various biochemical parameters were obtained from the medical records and medical history. Serum LPL, HL, and EL levels were detected by ELISA. The correlation between serum LPL, HL, and EL levels and coronary lesions was statistically analyzed with SPSS software. ResultsSignificant differences were observed in serum levels of HL and EL between the progression-free group and the progression group (HL, 75.5 ± 39.2 ng/mL vs. 125.1 ± 42.1 ng/mL, P < 0.05; EL, 139.2 ± 59.6 pg/mL vs. 175.1 ± 40.1 pg/mL, P < 0.05), while the difference in the LPL level was not significant (P > 0.05). Receiver operating characteristic curve (ROC) analysis showed that the area under the curve (AUC) values of LPL, HL, and EL were 0.506 (95% CI: 0.369–0.642, P = 0.9470), 0.792 (95% CI: 0.664–0.888, P < 0.0001), and 0.693 (95% CI: 0.553–0.811, P = 0.0095), respectively. Additionally, logistic regression analysis showed that the serum level of HL was an independent risk factor for coronary artery lesion progression. ConclusionSerum levels of EL and HL, but not the serum level of LPL, were positively correlated with the progression of CAD. The serum level of HL was an independent risk factor for the progression of CAD, while the serum level of EL or LPL was not an independent risk factor for the progression of CAD. For the diagnosis of CAD progression, the serum level of HL was better than the serum level of EL or LPL.

Lean maternal hyperglycemia alters offspring lipid metabolism and susceptibility to diet-induced obesity in mice†.

We previously developed a model of gestational diabetes mellitus (GDM) in which dams exhibit glucose intolerance, insulin resistance, and reduced insulin response to glucose challenge only during pregnancy, without accompanying obesity. Here, we aimed to determine how lean gestational glucose intolerance affects offspring risk of metabolic dysfunction. One cohort of offspring was sacrificed at 19 weeks, and one at 31 weeks, with half of the second cohort placed on a high-fat, high-sucrose diet (HFHS) at 23 weeks. Exposure to maternal glucose intolerance increased weights of HFHS-fed offspring. Chow-fed offspring of GDM dams exhibited higher body fat percentages at 4, 12, and 20 weeks of age. At 28 weeks, offspring of GDM dams fed the HFHS but not the chow diet (CD) also had higher body fat percentages than offspring of controls (CON). Exposure to GDM increased the respiratory quotient (Vol CO2/Vol O2) in offspring. Maternal GDM increased adipose mRNA levels of peroxisome proliferator-activated receptor gamma (Pparg) and adiponectin (Adipoq) in 31-week-old CD-fed male offspring, and increased mRNA levels of insulin receptor (Insr) and lipoprotein lipase (Lpl) in 31-week-old male offspring on both diets. In liver at 31 weeks, mRNA levels of peroxisome proliferator-activated receptor alpha (Ppara) were elevated in CD-fed male offspring of GDM dams, and male offspring of GDM dams exhibited higher mRNA levels of Insr on both diets. Neither fasting insulin nor glucose tolerance was affected by exposure to GDM. Our findings show that GDM comprising glucose intolerance only during pregnancy programs increased adiposity in offspring, and suggests increased insulin sensitivity of subcutaneous adipose tissue.

Regulatory roles of adiponectin receptor 1 and 2 in sheep preadipocytes during adipocyte differentiation

Adipose tissue has long been considered as an energy storage organ. Adipokines, produced by and secreted from adipose tissues, play an important role in regulating fat accumulation, energy balance, and glucose metabolism. Adiponectin receptors (AdipoR1 and AdipoR2) are expressed in various sheep tissues, including adipose tissue. However, the role of adiponectin receptor-mediated signalling has never been investigated in sheep adipose tissue. In this study, sheep preadipocytes were ultimately differentiated into typical adipocytes in vitro 7 days after differentiation. The expression levels of LPL (lipoprotein lipase), HSL (Hormone-sensitive lipase), FAS (fatty acid synthase), and PPARα/PPARγ (peroxisome proliferator-activated receptor alpha/gamma) were significantly changed in the sheep preadipocytes during differentiation for 7 days. After induction of preadipocyte differentiation, lipid accumulation increased significantly in the transfected preadipocytes of AdipoR1-siRNA1 but decreased in the AdipoR1-overexpression (AdipoR1-GFP) preadipocytes. In addition, the expression of HSL and PPARγ was significantly changed in preadipocytes by transfected with AdipoR1-siRNA1 or AdipoR1-GFP. However, the lipid accumulation and adipogenic gene expression were not significantly changed in preadipocytes by transfected with AdipoR2-siRNA2 and AdipoR2-GFP. Taken together, these results indicate that AdipoR1 could regulate sheep adipose metabolism via regulating HSL and PPARγ expression during adipocyte differentiation.HighlightsWe first established an in vitro culture system for sheep preadipocytes derived from the paraspinal muscle adipose.Sheep preadipocytes were ultimately differentiated into typical adipocytes after induction and differentiation.Both suppression and overexpression of adiponectin receptor 1 expression affect lipid accumulation and adipocyte metabolism during adipocyte differentiation.

Laparoscopic Sleeve Gastrectomy Significantly Increases Serum Lipoprotein Lipase Level in Obese Patients

Objectives: Obesity is one of the causes of metabolic disorders. Laparoscopic sleeve gastrectomy (LSG) confers beneficial effects not only on body weight (BW) but also on metabolic disorders. The lipoprotein lipase (LPL) level in preheparin serum is associated with visceral adipose tissue and reflects insulin resistance. However, the change in serum preheparin LPL levels after LSG remains unclear. This study aimed to examine the effect of LSG on preheparin LPL level in obese patients compared with nonsurgical treatment. Methods: We retrospectively reviewed a total of 100 obese patients who were treated for obesity and had preheparin LPL levels measured before and 12 months after LSG or after 12 months of nonsurgical treatment. Fifty-six patients received LSG (LSG group), and 44 patients had no surgical treatment (nonsurgical group). We compared clinical parameters such as body mass index (BMI), hemoglobin A_1c (HbA_1c), and preheparin LPL level before and 12 months after treatment. Results: BMI and HbA_1c decreased significantly in both groups, but decreases in both parameters were greater in the LSG group than in the nonsurgical group. Estimated glomerular filtration was significantly improved only in the LSG group. Preheparin LPL level increased significantly only in the LSG group (from 45.8 ± 21.6 to 75.0 ± 34.9 ng/mL, p < 0.001). Multiple regression identified LSG and decreased BMI as independent predictors of preheparin LPL level increase. Conclusions: These results suggest that LSG independently increases pre­heparin LPL level beyond BW reduction in obese patients.

GPIHBP1 autoantibody syndrome during interferon β1a treatment

Autoantibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) cause chylomicronemia by blocking the ability of GPIHBP1 to bind lipoprotein lipase (LPL) and transport the enzyme to its site of action in the capillary lumen. A patient with multiple sclerosis developed chylomicronemia during interferon (IFN) β1a therapy. The chylomicronemia resolved when the IFN β1a therapy was discontinued. Here, we sought to determine whether the drug-induced chylomicronemia was caused by GPIHBP1 autoantibodies. We tested plasma samples collected during and after IFN β1a therapy for GPIHBP1 autoantibodies (by western blotting and with enzyme-linked immunosorbent assays). We also tested whether the patient's plasma blocked the binding of LPL to GPIHBP1 on GPIHBP1-expressing cells. During IFN β1a therapy, the plasma contained GPIHBP1 autoantibodies, and those autoantibodies blocked GPIHBP1's ability to bind LPL. Thus, the chylomicronemia was because of the GPIHBP1 autoantibody syndrome. Consistent with that diagnosis, the plasma levels of GPIHBP1 and LPL were very low. After IFN β1a therapy was stopped, the plasma triglyceride levels returned to normal, and GPIHBP1 autoantibodies were undetectable. The appearance of GPIHBP1 autoantibodies during IFN β1a therapy caused chylomicronemia. The GPIHBP1 autoantibodies disappeared when the IFN β1a therapy was stopped, and the plasma triglyceride levels fell within the normal range.

PO-206 Effects of chemerin/CMKLR1 on aerobic exercise-induced improvement of glycolipid metabolism in atherosclerosis rats

Objective As an adipokine and inflammatory cytokines, chemerin plays an vital role in the occurrence and severity of obesity and its related disease such as atherosclerosis (AS), type 2 diabetes and coronary artery disease, among which the regulation of chemerin on glycolipid metabolism is of great important. Chemerin exerts its main biological functions through binding to its receptor: G protein-coupled receptor chemokine-like receptor (CMKLR1). Chemerin/CMKLR1 has become potential targets for diabetes treatment. For AS, the serum level of chemerin is also related to the disorders of glycolipid metabolism as well as the size and fibrous cap maturity of AS plaques. Exercise decreased the serum level of chemerin in AS, accompanied with the improvement of glucose and lipid metabolism, which indicated the possible relation between decrease of chemerin and improvement of glycolipid metabolism. However, it is still unclear whether exercise-induced improvements of glycolipid metabolism is associated with the changes of chemerin and CMKLR1 in tissue such as livers and gastrocnemius (play key roles in the modulation of glycolipid metabolism) and the mechanism by which chemerin/CMKLR1 modulated glycolipid metabolism. Recent studies reported that chemerin is a target gene of nuclear transcription factor- peroxisome proliferator activated receptor γ (PPARγ). PPARγ links glycolipid metabolism and inflammation through its target gene-adipose triglyceride lipase (ATGL) and lipoprotein lipase (LPL), gate-keeping enzymes hydrolyzing lipids in intracellular triglyceride and plasma lipoproteins respectively. Our previous work has found that aerobic exercise decreased the level of chemerin/CMKLR1 in serum and tissues of type 2 diabetes rats by the mediation of PPARγ-ATGL and LPL. So the purposes of this study were to clarify if exercise-modulated improvement of glycolipid metabolism of atherosclerosis rats was also associated with the changes of chemerin and CMKLR1 in serum and tissues (liver and gastrocnemius), similar as in diabetes, and further its mechanisms. &#x0D; Methods Twenty-seven male Sprague-Dawley (SD) rats aged 6 weeks were randomly divided into control group (Con, n=9) and atherosclerosis (AS, n=18) model rats. AS model rats were established by intraperitoneal injection of Vitamin D3 (600,000 IU/kg body weight in the first week, 100,000 IU/kg body weight in the third week and six week) in combination with 8-week high fat diet feeding. For verifying the successful establishment of AS rats, one rat from Con group and two rats from AS model group were taken randomly to determine the levels of blood glucose and lipid as well as the morphological and pathological alterations of the aorta. Then, 16 successfully established AS rats were randomly divided into AS group (n=8) and exercised AS group (EAS, n=8). EAS group rats experience 4-week moderate intensity aerobic exercise on treadmill with gradually increasing intensity, while the Con and AS rats were kept sedentary life, with all of the rats were fed with common diet during the experiments. Before and after 4-week exercise, the blood sample of the three group rats were drawn to measure the circulating levels of fasting blood glucose (FBG), triglyceride (TC), total cholesterol (TG), LDL and HDL. The serum fasting insulin (FINS) and serum chemerin were measured by ELISA. The protein levels of chemerin, CMKLR1, PPARγ, ATGL and LPL in livers and gastrocnemius were detected by Western blot. And the full-length aorta of the rats were separated to determine AS arteriosclerosis plaques with oil red O staining and histopathological examination with HE staining.&#x0D; &#x0D; Results 1) Compared with AS rats, the disorder of glycolipid metabolism (reflected&#x0D; by increases in TC, TG, LDL and FINS as well as decrease in HDL in blood although no difference in serum level of FBG) were all improved in EAS rats. 2) Compared with AS rats, the atherosclerotic plaque in the aoras and the enhanced proliferation and arrangement disorder of smooth muscle cells in aorta membrane were all alleviated in EAS rats. 3) Compared with AS rats, the increased chemerin in serum and the enhancements of chemerin and CMKLR1 in liver and gastrocnemius at protein levels were all significantly decreased in EAS rats. 4) Compared with AS rats, the protein levels of PPARγ, ATGL and LPL in the livers and gastrocnemius were all increased in EAS rats.&#x0D; Conclusions This study verified that: 1) the exercise-induced improvement of glycolipid metabolism in AS rats was likely to be associated with the decreases of chemerin in serum as well as of chemerin and CMKLR1 in tissues (liver and gastrocnemius). To our knowledge, it is the first report that exercise down-regulated chemerin/CMKLR1 in tissues in AS rats, and the decreases of chemerin/CMKLR1 might be related to the improvement of glycolipid metabolism in AS rats. 2) the exercise-induced decreases of chemerin/CMKLR1 in AS rats might be mediated by PPARγ and its target genes- ATGL and LPL, which need further investigations.

An ELISA for quantifying GPIHBP1 autoantibodies and making a diagnosis of the GPIHBP1 autoantibody syndrome

BackgroundAutoantibodies against GPIHBP1, the endothelial cell transporter for lipoprotein lipase (LPL), cause severe hypertriglyceridemia (“GPIHBP1 autoantibody syndrome”). Affected patients have low serum GPIHBP1 and LPL levels. We report the development of a sensitive and specific ELISA, suitable for routine clinical use, to detect GPIHBP1 autoantibodies in serum and plasma. MethodsSerum and plasma samples were added to wells of an ELISA plate that had been coated with recombinant human GPIHBP1. GPIHBP1 autoantibodies bound to GPIHBP1 were detected with an HRP-labeled antibody against human immunoglobulin. Sensitivity, specificity, and reproducibility of the ELISA was evaluated with plasma or serum samples from patients with the GPIHBP1 autoantibody syndrome. ResultsA solid-phase ELISA to detect and quantify GPIHBP1 autoantibodies in human plasma and serum was developed. Spiking recombinant human GPIHBP1 into the samples reduced the ability of the ELISA to detect GPIHBP1 autoantibodies. The ELISA is reproducible and sensitive; it can detect GPIHBP1 autoantibodies in samples diluted by >1000-fold. ConclusionWe have developed a sensitive and specific ELISA for detecting GPIHBP1 autoantibodies in human serum and plasma; this assay will make it possible to rapidly diagnose the GPIHBP1 autoantibody syndrome.