Lipoprotein Lipase Gene Expression Research Articles

Relationship between Lipoprotein Lipase Derived from Subcutaneous Adipose Tissue and Cardio-Ankle Vascular Index in Japanese Patients with Severe Obesity

Introduction: Cardio-ankle vascular index (CAVI) is an arterial stiffness index that correlates inversely with body mass index (BMI) and subcutaneous fat area. Lipoprotein lipase (LPL) that catalyzes the hydrolysis of serum triglycerides is produced mainly in adipocytes. Serum LPL mass reflects LPL expression in adipose tissue, and its changes correlate inversely with changes in CAVI. We hypothesized that LPL derived from subcutaneous adipose tissue (SAT) suppresses the progression of arteriosclerosis and examined the relationship of LPL gene expression in different adipose tissues and serum LPL mass with CAVI in Japanese patients with severe obesity undergoing laparoscopic sleeve gastrectomy (LSG). Methods: This study was a single-center retrospective database analysis. Fifty Japanese patients who underwent LSG and had 1-year postoperative follow-up data were enrolled (mean age 47.5 years, baseline BMI 46.6 kg/m2, baseline HbA1c 6.7%). SAT and visceral adipose tissue (VAT) samples were obtained during LSG surgery. LPL gene expression was analyzed by real-time PCR. Serum LPL mass was measured by ELISA using a specific monoclonal antibody against LPL. Results: At baseline, LPL mRNA expression in SAT correlated positively with serum LPL mass, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT was correlated, and serum LPL mass tended to correlate inversely with the number of metabolic syndrome symptoms, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT and CAVI tended to correlate inversely in the group with visceral-to-subcutaneous fat ratio of 0.4 or higher, which is considered metabolically severe. Serum LPL mass increased 1 year after LSG. Change in serum LPL mass at 1 year after LSG tended to be an independent factor inversely associated with change in CAVI. Conclusions: Serum LPL mass reflected LPL mRNA expression in SAT in Japanese patients with severe obesity, and LPL mRNA expression in SAT was associated with CAVI in patients with visceral obesity. The change in serum LPL mass after LSG tended to independently contribute inversely to the change in CAVI. This study suggests that LPL derived from SAT may suppress the progression of arteriosclerosis.

Dietary bile acids supplementation improves the growth performance and alleviates fatty liver in broilers fed a high-fat diet via improving the gut microbiota

This experiment aims to evaluate the effect of bile acids (BAs) in alleviating fatty liver disease induced by a high-fat diet (HFD) in broilers, and the modulation of the gut microbiota involved in this process. A total of 192 one-day-old Arbor Acres (AA) commercial male broilers were randomly divided into 4 groups and treated with the following diet: a basal-fat diet (BFD), a basal-fat diet plus bile acids (BFD + BAs), an HFD, and a high-fat diet plus bile acids (HFD + BAs). Bile acids were supplemented at the early growth stage (3-7 d), middle stage (17-21 d), and late stage (31-35 d). Results showed that BAs treatment had a significant effect on body weight on 14 d and 35 d, and increased the breast muscle weight and its index, but decreased the liver weight and abdominal fat weight on 35 d (P < 0.05). The supplementation of BAs significantly improved the serum lipid profile and decreased the level of triglycerides (TG), total cholesterol (TCHO), and nonesterified fatty acids (NEFA) on 35 d (P < 0.05). Dietary BAs supplementation significantly alleviated the hepatic TG deposition induced by HFD (P < 0.05), which was accompanied by upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) gene expression (P < 0.05). Moreover, the expression levels of hepatic gene adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor α (PPARα), and apolipoprotein B (APOB) were greatly increased by BAs treatment. The analysis of 16S rRNA sequencing showed that the microbial diversity of the cecal digesta was increased by BAs in broilers with elevated abundances of Firmicutes, Lactobacillus, Anaerostipes, Sellimonas, and CHKCI002 and decreased abundances of Barnesiella and Akkermansia genus (P < 0.05). Hepatic TG content was positively correlated with the abundance of Oscillospiraceae, but it was negatively correlated with the abundance of Lactobacillus in cecal digesta (P < 0.05). These results indicate that dietary BAs can improve growth performance and alleviate fatty liver disease induced by an HFD via modulating gut microbiota in broilers.

Effects of Dietary Steroid Saponins on Growth Performance, Serum and Liver Glucose, Lipid Metabolism and Immune Molecules of Hybrid Groupers (♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatu) Fed High-Lipid Diets.

High-lipid diets are attributed to excessive lipid deposition and metabolic disturbances in fish. The aim of this experiment was to investigate the effects of steroidal saponins on growth performance, immune molecules and metabolism of glucose and lipids in hybrid groupers (initial weight 22.71 ± 0.12 g) fed high-lipid diets. steroidal saponins (0%, 0.1% and 0.2%) were added to the basal diet (crude lipid, 14%) to produce three experimental diets, designated S0, S0.1 and S0.2, respectively. After an 8-week feeding trial, no significant differences were found between the S0 and S0.1 groups in percent weight gain, specific growth rate, feed conversion ratio, protein efficiency ratio and protein deposition rate (p > 0.05). All those in the S0.2 group were significantly decreased (p < 0.05). Compared to the S0 group, fish in the S0.1 group had lower contents of serum triglyceride and low-density lipoprotein cholesterol and higher high-density lipoprotein cholesterol and glucose (p < 0.05). The activities of superoxide dismutase, catalase and glutathione peroxidase were significantly higher, and malondialdehyde contents were significantly lower in the S0.1 group than in the S0 group (p < 0.05). Hepatic triglyceride, total cholesterol and glycogen were significantly lower in the S0.1 group than in the S0 group (p < 0.05). Activities of lipoprotein lipase, total lipase, glucokinase and pyruvate kinase, and gene expression of lipoprotein lipase, triglyceride lipase and glucokinase, were significantly higher in the S0.1 group than in the S0 group. Interleukin-10 mRNA expression in the S0.1 group was significantly higher than that in the S0 group, while the expression of interleukin-6 and tumor necrosis factor-α genes were significantly lower than those in the S0 group. In summary, adding 0.1% steroidal saponins to a high-lipid diet not only promoted lipolysis in fish livers, but also activated glycolysis pathways, thus enhancing the utilization of the dietary energy of the groupers, as well as supporting the fish's nonspecial immune-defense mechanism.

Apolipoprotein H: a novel regulator of fat accumulation in duck myoblasts

Apolipoprotein H (APOH) primarily engages in fat metabolism and inflammatory disease response. This study aimed to investigate the effects of APOH on fat synthesis in duck myoblasts (CS2s) by APOH overexpression and knockdown. CS2s overexpressing APOH showed enhanced triglyceride (TG) and cholesterol (CHOL) contents and elevated the mRNA and protein expression of AKT serine/threonine kinase 1 (AKT1), ELOVL fatty acid elongase 6 (ELOVL6), and acetyl-CoA carboxylase 1 (ACC1) while reducing the expression of protein kinase AMP-activated catalytic subunit alpha 1 (AMPK), peroxisome proliferator activated receptor gamma (PPARG), acyl-CoA synthetase long chain family member 1 (ACSL1), and lipoprotein lipase (LPL). The results showed that knockdown of APOH in CS2s reduced the content of TG and CHOL, reduced the expression of ACC1, ELOVL6, and AKT1, and increased the gene and protein expression of PPARG, LPL, ACSL1, and AMPK. Our results showed that APOH affected lipid deposition in myoblasts by inhibiting fatty acid beta-oxidation and promoting fatty acid biosynthesis by regulating the expression of the AKT/AMPK pathway. This study provides the necessary basic information for the role of APOH in fat accumulation in duck myoblasts for the first time and enables researchers to study the genes related to fat deposition in meat ducks in a new direction.

The Different Insulin-Sensitising and Anti-Inflammatory Effects of Palmitoleic Acid and Oleic Acid in a Prediabetes Model.

Introduction Monounsaturated fatty acids (MUFA) are understood to have therapeutic and preventive effects on chronic complications associated with type 2 diabetes mellitus (T2DM); however, there are differences between individual MUFAs. Although the effects of palmitoleic acid (POA) are still debated, POA can regulate glucose homeostasis, lipid metabolism, and cytokine production, thus improving metabolic disorders. In this study, we investigated and compared the metabolic effects of POA and oleic acid (OA) supplementation on glucose and lipid metabolism, insulin sensitivity, and inflammation in a prediabetic model, the hereditary hypertriglyceridemic rat (HHTg). HHTg rats exhibiting genetically determined hypertriglyceridemia, insulin resistance, and impaired glucose tolerance were fed a standard diet. POA and OA were each administered intragastrically at a dose of 100 mg/kg b.wt. for four weeks. Results Supplementation with both MUFAs significantly elevated insulin and glucagon levels, but only POA decreased nonfasting glucose. POA-treated rats showed elevated circulating NEFA associated with increased lipolysis, lipoprotein lipase gene expression, and fatty acid reesterification in visceral adipose tissue (VAT). The mechanism of improved insulin sensitivity of peripheral tissues (measured as insulin-stimulated lipogenesis and glycogenesis) in POA-treated HHTg rats could contribute increased circulating adiponectin and omentin levels together with elevated FADS1 gene expression in VAT. POA-supplemented rats exhibited markedly decreased proinflammatory cytokine production by VAT, which can alleviate chronic inflammation. OA-supplemented rats exhibited decreased arachidonic acid (AA) profiles and decreased proinflammatory AA-derived metabolites (20-HETE) in membrane phospholipids of peripheral tissues. Slightly increased FADS1 gene expression after OA along with increased adiponectin production by VAT was reflected in slightly ameliorated adipose tissue insulin sensitivity (increased insulin-stimulated lipogenesis). Conclusions Our results show that POA served as a lipokine, ameliorating insulin sensitivity in peripheral tissue and markedly modulating the metabolic activity of VAT including cytokine secretion. OA had a beneficial effect on lipid metabolism and improved inflammation by modulating AA metabolism.

Exogenous butyrate regulates lipid metabolism through GPR41-ERK-AMPK pathway in rabbits

Diets containing higher levels of fat can lead to obesity, which is potentially harmful to health. Endogenous butyric acid is produced by intestinal microbial fermentation and participates in lipid metabolism. However, there is less butyric acid produced in the body, butyric acid has a shorter half-life in the blood. We used intraperitoneal injection of sodium butyrate to study the mechanism of butyrate involved in body lipid metabolism. Triglycerides in adipose tissue and liver were significantly reduced by butyrate. The content of triglyceride in plasma in butyrate group was also significantly decreased. In adipose tissue, butyrate up-regulated gene expression of hormone-sensitive lipase (HSL), carnitine palmitoyl transferase (CPT)1 and CPT2, and increased protein expression of G protein-coupled receptor (GPR)41, phosphorylated extracellular-signal-regulated kinase (P-ERK), adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and P-AMPK. Gene expression of lipoprotein lipase (LPL), differentiation-dependent factor 1 (ADD1) and fatty acid synthase (FAS) was down-regulated. In liver, butyrate up-regulated protein expression of GPR41, ERK, P-ERK, P-AMPK. Gene expression of ADD1 and FAS was down-regulated. In muscle tissue, butyrate significantly up-regulated the expression of gene LPL, fatty acid transport protein (FATP) and fatty acid-binding protein (FABP) and protein GPR41, GPR43. Thus, butyrate is involved in body lipid metabolism mainly through the GPR41-mediated ERK-AMPK pathway. Inhibits lipid synthesis in adipose tissue and the liver and promotes lipolysis, avoiding obesity caused by diets with higher fat content. Highlights Butyrate affects lipid metabolism in the body by affecting lipid synthesis/decomposition in adipose tissue and liver. Butyrate mainly through GPR41-mediated ERK-AMPK pathway, inhibit lipid synthesis, promote lipid decomposition, and avoid a large amount of fat accumulation induced by higher-fat diet.

Expression of lipoprotein lipase and SORL1 genes in patients with chronic lymphocytic leukemia

Introduction. Leukemic cells of patients with chronic lymphocytic leukemia (CLL) are characterized by high expression of the lipoprotein lipase (LPL) gene in unmutated (UM) status of the variable region of the immunoglobulin heavy chain (IGHV) genes and low expression of the SORL1 gene. SORL1 protein promotes the degradation of LPL in nervous cells in vitro that has been previously shown. Objective: to study SORL1 gene expression in CLL patients depending on LPL gene expression and mutational status of IGHV genes. Materials and methods. Analysis was performed in the group of 61 CLL patients. The IGHV gene mutational status was studied by polymerase chain reaction (PCR) followed by direct sequencing. LPL and SORL1 expression was evaluated by Quantitative Real-time PCR. Results. Relative LPL expression levels in CLL samples ranged from 0.5 to 119.5 (mean 23.65 ± 5.19) and correlated with IGHV mutational status (p &lt; 0.01). The average relative SORL1 expression level was 1.71 ± 0.55. No association between SORL1 expression and IGHV mutational status was found (p = 0.358). Among unmutated IGHV cases, negative correlation between LPL and SORL1 gene expression levels was identified (r = -0.764; p = 0.036). Conclusion. The obtained data support the involvement of SORL1 in the post-translational regulation of LPL levels in leukemic cells in CLL. Ketwords: chronic lymphocytic leukemia, lipoprotein lipase, SORL1.

Bisphenol F and bisphenol S promote lipid accumulation and adipogenesis in human adipose-derived stem cells

Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as substitutes for bisphenol A (BPA), an endocrine disrupting chemical (EDC) with obesogenic activity. We investigated the in vitro effects of BPS and BPF on the adipogenesis of human adipose-derived stem cells (hASCs) exposed to different doses (0.01, 0.1, 1, 10 and 25 μM), stopping the adipogenic process at 7 or 14 days. Intracellular lipid accumulation was quantified by the Oil Red O assay, gene expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAT/enhancer-binding protein (C/EBPα), lipoprotein-lipase (LPL) and fatty acid binding protein 4 (FABP4), by quantitative real-time polymerase chain reaction (qRT-PCR) and protein levels by Western Blot. hASCs with BPF or BPS produced a linear dose-response increase in intracellular lipid accumulation and in gene expression of the adipogenic markers, confirmed by protein levels. Co-treatment ICI 182,780 significantly inhibited BPF- but not BPS-induced lipid accumulation. Given the affinity of bisphenols for diverse nuclear receptors, their obesogenic effects may result from a combination of pathways rather than a single mechanism. Further research is warranted on the manner in which chemicals interfere with adipogenic differentiation. To our best knowledge, this report shows for the first time the obesogenic potential of BPF in hASCs.

Liraglutide Increases the Catabolism of Apolipoprotein B100-Containing Lipoproteins in Patients With Type 2 Diabetes and Reduces Proprotein Convertase Subtilisin/Kexin Type 9 Expression.

Dyslipidemia observed in type 2 diabetes (T2D) is atherogenic. Important features of diabetic dyslipidemia are increased levels of triglyceride-rich lipoproteins and small dense LDL particles, which all have apolipoprotein B100 (apoB100) as a major apolipoprotein. This prompted us to study the effect of the GLP-1 agonist liraglutide on the metabolism of apoB100-containing lipoproteins. We performed an in vivo kinetic study with stable isotopes (L-[1-13C]leucine) in 10 patients with T2D before and after 6 months of treatment with liraglutide (1.2 mg/day). We also evaluated in mice the effect of liraglutide on the expression of genes involved in apoB100-containing lipoprotein clearance. In patients with T2D, liraglutide treatment significantly reduced plasma apoB100 (0.93 ± 0.13 vs. 1.09 ± 0.11 g/L, P = 0.011) and fasting triglycerides (1.76 ± 0.37 vs. 2.48 ± 0.69 mmol/L, P = 0.005). The kinetic study showed a significant increase in indirect catabolism of VLDL1-apoB100 (4.11 ± 1.91 vs. 2.96 ± 1.61 pools/day, P = 0.005), VLDL2-apoB100 (5.17 ± 2.53 vs. 2.84 ± 1.65 pools/day, P = 0.008), and IDL-apoB100 (5.27 ± 2.77 vs. 3.74 ± 1.85 pools/day, P = 0.017) and in catabolism of LDL-apoB100 (0.72 ± 0.22 vs. 0.56 ± 0.22 pools/day, P = 0.005). In mice, liraglutide increased lipoprotein lipase (LPL) gene expression and reduced proprotein convertase subtilisin/kexin type 9 (PCSK9), retinol-binding protein 4 (RBP4), and tumor necrosis factor-α (TNF-α) gene expression in adipose tissue and decreased PCSK9 mRNA and increased LDL receptor protein expression in liver. In vitro, liraglutide directly reduced the expression of PCSK9 in the liver. Treatment with liraglutide induces a significant acceleration of the catabolism of triglyceride-rich lipoproteins (VLDL1, VLDL2, IDL) and LDL. Liraglutide modifies the expression of genes involved in apoB100-containing lipoprotein catabolism. These positive effects on lipoprotein metabolism may reduce cardiovascular risk in T2D.

The Digestive Function of Pseudoplatystoma punctifer Early Juveniles Is Differentially Modulated by Dietary Protein, Lipid and Carbohydrate Content and Their Ratios.

Pseudoplatystoma punctifer is an Amazonian catfish highly appreciated for its high flesh quality, size, and commercial value. Its aquaculture is pursued to satisfy the demands of an increasing population in the region. However, knowledge of the nutritional needs during the early life stages is necessary for improving growth and reducing the incidence of cannibalism, factors that limit the success of its commercial farming. This study aimed at evaluating the influence of four diets containing different protein and lipid levels (30:15, 30:10, 45:15, or 45:10 in %) in the digestive physiology and performance of early juveniles. The results showed that the dietary protein:lipid as well as carbohydrate levels and ratios influenced differently the whole-body proximate composition, the digestive physiology and development, and hence growth and survival. The 45:15 diet promoted the best growth, survival, and the most rapid development of the digestive system, as shown at histological (higher number of hepatocytes, goblet cells in the anterior intestine and enterocytes in all intestinal portions, and longer folds in the posterior intestine), molecular (highest amylase, lipoprotein lipase, phospholipase, trypsinogen, and pepsinogen gene expression), and biochemical (highest lipase and pepsin activities and higher alkaline phosphatase:leucine alanine peptidase activity ratio) levels. Lipids were favored over carbohydrates as source of energy, with lipids promoting a protein-sparing effect at adequate energy:protein ratio. Carbohydrate content higher than 25% was excessive for this species, leading to unbalanced lipid metabolism and fat deposition in the liver.

Effects of dietary fat source and green tea (Camellia sinensis) extract on genes associated with lipid metabolism and inflammatory responses in female broiler chickens

This study was aimed to investigate the effects of dietary fat sources and green tea extract (GTE) on gene expression associated with lipid metabolism and inflammation in broiler chicken. A total of 300 female Ross 308 broiler chicks were allocated to six dietary treatments in a completely randomised design with a factorial arrangement of two levels of GTE (0 and 500 mg/kg diet) × three levels of fat inclusion [without fat (control group), soybean oil (SO) and tallow (Ta)]. Liver fat (LF), liver methallothionin (LMT) content, and lipoprotein lipase (LPL), adipose triglyceride lipase (ATGL), tumour necrosis factor α (TNF-α), and interleukin (IL-6)] genes expression were investigated. Relative expression and statistical analyses of genes expression were assessed using REST software. The effect of added dietary fats was significant and improved performance parameters compared to the control group (p < .05). The highest abdominal fat and blood triglyceride, and the lowest carcase yield, were achieved in chicks fed SO-supplemented diet (p < .05). Chicks fed a diet supplemented with SO showed an overexpression and a decrease of LPL and ATGL compared to the Ta-supplemented and control groups, respectively (p < .05). GTE supplementation was effective on LPL and ATGL expression and ameliorated the effect of SO on abdominal fat percentage. TNF-α expression, LMT content, and relative weight of lymphoid organs were affected neither by GTE nor by the fat sources. There was no detection of IL-6 gene expression in adipose tissue. The results of this study demonstrated that diets rich in SO were capable increase fat deposition by an increase and decrease in LPL and ATGL gene expression, respectively. However inclusion of GTE in broiler diets alleviated the LPL-increasing and ATGL-reducing effects of SO and ameliorated the effect of SO on abdominal fat mass. Highlights Diets supplemented with SO increased abdominal fat mass by changes in LPL and ATGL gene expression. Obesity was not effective in the expression of inflammatory genes (TNF-α and IL-6), indicating a lack of connection between inflammation and obesity in broiler chicken. GTE (500 mg/kg diet) addition to the diets supplemented with SO ameliorated the effect of SO on LPL and ATGL gene expression and abdominal fat mass.

Flight training in a migratory bird drives metabolic gene expression in the flight muscle but not liver, and dietary fat quality influences select genes.

Training and diet are hypothesized to directly stimulate key molecular pathways that mediate animal performance, and flight training, dietary fats, and dietary antioxidants are likely important in modulating molecular metabolism in migratory birds. This study experimentally investigated how long-distance flight training, as well as diet composition, affected the expression of key metabolic genes in the pectoralis muscle and the liver of European starlings (Sturnus vulgaris, n = 95). Starlings were fed diets composed of either a high or low polyunsaturated fatty acid (PUFA; 18:2n-6) and supplemented with or without a water-soluble antioxidant, and one-half of these birds were flight trained in a wind-tunnel while the rest were untrained. We measured the expression of 7 (liver) or 10 (pectoralis) key metabolic genes in flight-trained and untrained birds. Fifty percent of genes involved in mitochondrial metabolism and fat utilization were upregulated by flight training in the pectoralis (P < 0.05), whereas flight training increased the expression of only one gene responsible for fatty acid hydrolysis [lipoprotein lipase (LPL)] in the liver (P = 0.04). Dietary PUFA influenced the gene expression of LPL and fat transporter fatty acid translocase (CD36) in the pectoralis and one metabolic transcription factor [peroxisome proliferator-activated receptor (PPAR)-α (PPARα)] in the liver, whereas dietary antioxidants had no effect on the metabolic genes measured in this study. Flight training initiated a simpler causal network between PPARγ coactivators, PPARs, and metabolic genes involved in mitochondrial metabolism and fat storage in the pectoralis. Molecular metabolism is modulated by flight training and dietary fat quality in a migratory songbird, indicating that these environmental factors will affect the migratory performance of birds in the wild.

Regulation of glucose and lipid metabolism by insulin and glucagon in vivo and in vitro in common carp Cyprinus carpio L.

Our objective is to study the low metabolic utilization of dietary carbohydrates in fish. The regulation of key enzymes involved in glucose and lipid metabolism in the common carp (Cyprinus carpio L.), known to be relatively tolerant to dietary carbohydrates, were assessed. We performed intraperitoneal (i.p.) administration of insulin and glucagon to common carp and also subjected common carp primary hepatocytes to insulin or glucagon. The results showed that insulin administration induced hypoglycaemia through up-regulation of the expression of the glycolysis genes glucokinase (GK) and hexose kinase (HK), coupled with increased gene expression of fatty acid synthase (FAS), acetyl-CoA carboxylase-1 (ACC-1), sterol-regulator element-binding protein-1 (SREBP-1). Insulin also limited the expression of the gluconeogenesis genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), coupled with decreased gene expression of lipoprotein lipase (LPL) and carnitine palmitoyl transferase I (CPT-1). However, glucagon had the opposite effect. The results showed that glucagon induced hyperglycemia with increased expression of PEPCK and G6Pase and increased lipolytic capacity as indicated by lower mRNA levels of SREBP-1. Glucagon (i.p.) significantly increased the activity of PEPCK and LPL in hepatopancreas. In addition, the mRNA expression of HK showed an up-regulated trend and the mRNA expression of PEPCK and G6Pase showed a down-regulated trend in the group of glucose (i.p.). This study demonstrates that insulin and glucagon possess the intrinsic ability to regulate hepatic energy metabolism in common carp, the regulation of which seems to be similar to that of the mammals at least at the molecular level.

Fasting induces ANGPTL4 and reduces LPL activity in human adipose tissue

ObjectiveStudies in mice have shown that the decrease in lipoprotein lipase (LPL) activity in adipose tissue upon fasting is mediated by induction of the inhibitor ANGPTL4. Here, we aimed to validate this concept in humans by determining the effect of a prolonged fast on ANGPTL4 and LPL gene and protein expression in human subcutaneous adipose tissue. MethodsTwenty-three volunteers ate a standardized meal at 18.00 h and fasted until 20.00 h the next day. Blood was drawn and periumbilical adipose tissue biopsies were collected 2 h and 26 h after the meal. ResultsConsistent with previous mouse data, LPL activity in human adipose tissue was significantly decreased by fasting (−60%), concurrent with increased ANGPTL4 mRNA (+90%) and decreased ANGPTL8 mRNA (−94%). ANGPTL4 protein levels in adipose tissue were also significantly increased by fasting (+46%), whereas LPL mRNA and protein levels remained unchanged. In agreement with the adipose tissue data, plasma ANGPTL4 levels increased upon fasting (+100%), whereas plasma ANGPTL8 decreased (−79%). Insulin, levels of which significantly decreased upon fasting, downregulated ANGPTL4 mRNA and protein in primary human adipocytes. By contrast, cortisol, levels of which significantly increased upon fasting, upregulated ANGPTL4 mRNA and protein in primary human adipocytes as did fatty acids. ConclusionANGPTL4 levels in human adipose tissue are increased by fasting, likely via increased plasma cortisol and free fatty acids and decreased plasma insulin, resulting in decreased LPL activity.This clinical trial was registered with identifier NCT03757767.

Effects of waterborne exposure to 17β-estradiol on hepatic lipid metabolism genes in tilapia (Oreochromis niloticus)

Estradiol is a steroid hormone that regulates multiple physiological processes in teleosts. The present study aimed to investigate the role of 17β-estradiol (E2) in lipid metabolism in the liver of Nile tilapia. Waterborne exposures were performed using different concentrations of E2 (0 ng/L, 10 ng/L, 25 ng/L and 50 ng/L) and its receptor inhibitor ICI 182,780 (ICI) (1 μM/L). Subsequently, the survival rate and hepatosomatic index (HSI) of tilapia were measured and no significant changes could be found following E2 exposure. Gene expression of VLDL assembly, lipoprotein lipase and lipoprotein receptor, fatty acid uptake and triacylglycerol metabolism were detected by qPCR. E2 exposure up-regulated the expression of lipid metabolism-related genes MTP, LPL, CD36 and DGAT2. ICI exposure inhibited the level of LDLR in the liver of tilapia. This showed that E2 stimulated the MTP expression and promoted VLDL synthesis. In addition, E2 waterborne exposure induced secretion of LDLR and LPL and promoted fatty acid production. Moreover, E2 up-regulated the expression of CD36 to accelerate the transport of fatty acids. Overall, our study provides new information for evaluating Environmental estrogens (EEs) effects on farming fishes and endocrinological regulation on lipid metabolism in fish.

Body condition and insulin resistance interactions with periparturient gene expression in adipose tissue and lipid metabolism in dairy cows

Adipose tissue plays an important role in a cow's ability to adapt to the metabolic demands of lactation, because of its central involvement in energy metabolism and immunity. High adiposity and adipose tissue resistance to insulin are associated with excessive lipid mobilization. We hypothesized that the response to a glucose challenge differs between cows of different body condition 21 d before and after calving and that the responses are explainable by gene expression in subcutaneous adipose tissue (SAT). In addition, we aimed to investigate insulin resistance with gene expression in SAT and lipid mobilization around parturition. Multiparous Holstein cows were grouped according to body conditions score (BCS) 4 wk before calving, as follows: BCS ≤ 3.0 = thin (T, n = 14); BCS 3.25 to 3.5 = optimal (O, n = 14); BCS ≥ 3.75 = over-conditioned (OC, n = 14). We collected SAT on d -21 and d 21 relative to calving. A reverse-transcriptase quantitative (RT-q)PCR was used to measure gene expression related to lipid metabolism. One hour after the collection of adipose tissue, an intravenous glucose tolerance test was carried out, with administration of 0.15 g of glucose per kg of body weight (with a 40% glucose solution). Once weekly from the first week before calving to the third week after calving, a blood sample was taken. The transition to lactation was associated with intensified release of energy stored in adipose tissue, a decrease in the lipogenic genes lipoprotein lipase (LPL) and diacylglycerol O-acyltransferase 2 (DGAT2), and an increase in the lipolytic gene hormone-sensitive lipase (LIPE). On d -21, compared with T cows, OC cows had lower mRNA abundance of LPL and DGAT2, and the latency of fatty acid response after glucose infusion was also longer (8.5 vs. 23.3 min) in OC cows. Cows with higher insulin area under the curve on d -21 had concurrently lower LPL and DGAT2 gene expression and greater concentration of fatty acids on d -7, d 7, and d 14. In conclusion, high adiposity prepartum lowers the whole-body lipid metabolism response to insulin and causes reduced expression of lipogenic genes in SAT 3 weeks before calving. In addition, more pronounced insulin release after glucose infusion on d -21 is related to higher lipid mobilization around calving, indicating an insulin-resistant state, and is associated with lower expression of lipogenic genes in SAT.

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.

Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 and angiopoietin-like protein 4 are associated with the increase of lipoprotein lipase activity in epicardial adipose tissue from diabetic patients

Background and aimsEpicardial adipose tissue (EAT) is a visceral AT, surrounding myocardium and coronary arteries. Its volume is higher in Type 2 diabetic (DM2) patients, associated with cardiovascular disease risk. Lipoprotein lipase (LPL) hydrolyses triglycerides (TG) from circulating lipoproteins, supplying fatty acids to AT, contributing to its expansion. We aimed to evaluate LPL expression and activity in EAT from DM2 and no DM2 patients, and its regulators ANGPTL4, GPIHBP1 and PPARγ levels, together with VLDLR expression and EAT LPL association with VLDL characteristics. MethodsWe studied patients undergoing coronary by-pass graft (CABG) divided into CABG-DM2 (n = 21) and CABG-noDM2 (n = 29), and patients without CABG (No CABG, n = 30). During surgery, EAT and subcutaneous AT (SAT) were obtained, in which LPL activity, gene and protein expression, its regulators and VLDLR protein levels were determined. Isolated circulating VLDLs were characterized. ResultsEAT LPL activity was higher in CABG-DM2 compared to CABG-noDM2 and No CABG (p=0.002 and p<0.001) and in CABG-noDM2 compared to No CABG (p=0.02), without differences in its expression. ANGPTL4 levels were higher in EAT from No CABG compared to CABG-DM2 and CABG-noDM2 (p<0.001). GPIHBP1 levels were higher in EAT from CABG-DM2 and CABG-noDM2 compared to No CABG (p= 0.04). EAT from CABG-DM2 presented higher PPARγ levels than CABG-noDM2 and No CABG (p=0.02 and p=0.03). No differences were observed in VLDL composition between groups, although EAT LPL activity was inversely associated with VLDL-TG and TG/protein index (p<0.05). ConclusionsEAT LPL regulation would be mainly post-translational. The higher LPL activity in DM2 could be partly responsible for the increase in EAT volume.

Lipoprotein Lipase Inhibitor, Nordihydroguaiaretic Acid, Aggravates Metabolic Phenotypes and Alters HDL Particle Size in the Western Diet-Fed db/db Mice.

Lipoprotein lipase (LPL) hydrolyzes triglycerides in lipoprotein to supply fatty acids, and its deficiency leads to hypertriglyceridemia, thereby inducing metabolic syndrome (MetSyn). Nordihydroguaiaretic acid (NDGA) has been recently reported to inhibit LPL secretion by endoplasmic reticulum (ER)-Golgi redistribution. However, the role of NDGA on dyslipidemia and MetSyn remains unclear. To address this question, leptin receptor knock out (KO)-db/db mice were randomly assigned to three different groups: A normal AIN76-A diet (CON), a Western diet (WD) and a Western diet with 0.1% NDGA and an LPL inhibitor, (WD+NDGA). All mice were fed for 12 weeks. The LPL inhibition by NDGA was confirmed by measuring the systemic LPL mass and adipose LPL gene expression. We investigated whether the LPL inhibition by NDGA alters the metabolic phenotypes. NDGA led to hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. More strikingly, the supplementation of NDGA increased the percentage of high density lipoprotein (HDL)small (HDL3a+3b+3c) and decreased the percentage of HDLlarge (HDL2a+2b) compared to the WD group, which indicates that LPL inhibition modulates HDL subclasses. was NDGA increased adipose inflammation but had no impact on hepatic stress signals. Taken together, these findings demonstrated that LPL inhibition by NDGA aggravates metabolic parameters and alters HDL particle size.

Phenolic-enriched raspberry fruit extract (Rubus idaeus) resulted in lower weight gain, increased ambulatory activity, and elevated hepatic lipoprotein lipase and heme oxygenase-1 expression in male mice fed a high-fat diet

Red raspberries (Rubus idaeus) contain numerous phenolic compounds with purported health benefits. Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is a primary raspberry flavor phenolic found in raspberries and is designated as a synthetic flavoring agent by the Food and Drug Administration. Synthetic raspberry ketone has been demonstrated to result in weight loss in rodents. We tested whether phenolic-enriched raspberry extracts, compared with raspberry ketone, would be more resilient to the metabolic alterations caused by an obesogenic diet. Male C57BL/6J mice (8 weeks old) received a daily oral dose of vehicle (VEH; 50% propylene glycol, 40% water, and 10% dimethyl sulfoxide), raspberry extract low (REL; 0.2 g/kg), raspberry extract high (REH; 2 g/kg), or raspberry ketone (RK; 0.2 g/kg). Coincident with daily dosing, mice were placed on a high-fat diet (45% fat). After 4 weeks, REH and RK reduced body weight gain (approximately 5%-9%) and white adipose mass (approximately 20%) compared with VEH. Hepatic gene expression of heme oxygenase-1 and lipoprotein lipase was upregulated in REH compared with VEH. Indirect calorimetry indicated that respiratory exchange ratio (CO2 production to O2 consumption) was lower, suggesting increased fat oxidation with all treatments. REH treatment increased total ambulatory behavior. Energy expenditure/lean mass was higher in REH compared with REL treatment. There were no treatment differences in cumulative intake, meal patterns, or hypothalamic feed-related gene expression. Our results suggest that raspberry ketone and a phenolic-enriched raspberry extract both have the capacity to prevent weight gain but differ in the preventative mechanisms for excess fat accumulation following high-fat diet exposure.