Lipoprotein Lipase Levels Research Articles

Purple Corn Anthocyanin Affects Lipid Mechanism, Flavor Compound Profiles, and Related Gene Expression of Longissimus Thoracis et Lumborum Muscle in Goats.

Simple SummaryNatural flavor compounds can stimulate people’s senses of smell and taste; as indicators of food sensory quality, such compounds influence the acceptance by consumers. In addition, natural antioxidants are becoming popular among consumers because they are safe and have no adverse side effects. Purple corn anthocyanins are polyphenolic compounds with natural antioxidant properties that exist widely in nature. Research has shown that anthocyanins can provide extra electrons to the free radicals, preventing lipid oxidation and improving muscle volatile components. However, no information is available concerning the effect of feeding anthocyanin on goat meat volatile compounds. This was the first study to investigate the effects of dietary anthocyanins from purple corn supplementation on lipid mechanism, body composition, volatile compound profiles, and related gene expression in the longissimus thoracis et lumborum muscle of goats. The current study indicates that the consumption of purple corn anthocyanin by growing goats improves mutton flavor by decreasing plasma lipid metabolism parameters and by modulating the abundance of several flavor-related genes in the longissimus thoracis et lumborum muscle. The results will help to understand the mechanism of action of anthocyanins on the flavor compounds, providing the rationale for anthocyanins regulating mutton flavor through related signaling pathways of ruminants in future studies.The current study aimed to investigate the effect of anthocyanins on muscle flavor compound profiles in goats. Goats in three groups were fed a basic diet or a diet supplemented with 0.5 g/d or 1 g/d anthocyanin-rich purple corn pigment (PCP). Compared to the control group, plasma total cholesterol was significantly decreased (p < 0.05) in the anthocyanin groups. The feeding of anthocyanin increased (p < 0.05) flavor compound types and total alcohol level, whereas it decreased (p < 0.05) total hydrocarbons, aromatics, esters, and miscellaneous compounds in the longissimus thoracis et lumborum muscle (LTL). Adding PCP to the diet enriched (p < 0.05) vegetal, herbaceous, grease, and fruity flavors compared to the control group. The 0.5 g/d PCP group had increased (p < 0.05) abundance of peroxisome proliferator-activated receptor gamma, but there was a decreased (p < 0.05) level of lipoprotein lipase in LTL. Collectively, this study indicated that anthocyanin can improve mutton flavor by decreasing plasma lipid parameters and by modulating the abundance of several flavor-related genes of goats.

Association between ANGPTL3, 4, and 8 and lipid and glucose metabolism markers in patients with diabetes.

Lipid management, especially with respect to triglyceride (TG) metabolism, in patients with diabetes is not sufficient with current therapeutic agents, and new approaches for improvement are needed. Members of the angiopoietin-like protein (ANGPTL) family, specifically ANGPTL3, 4, and 8, have been reported as factors that inhibit lipoprotein lipase (LPL) activity and affect TGs. The present study investigated the association between lipid and glucose metabolism markers and the mechanism by which these proteins affect lipid metabolism. A total of 84 patients hospitalized for diabetes treatment were evaluated. Lipid and glucose metabolism markers in blood samples collected before breakfast, on the day after hospitalization, were analyzed. ANGPTL8 showed a significant positive correlation with TG values. HDL-C values displayed a significant positive correlation with ANGPTL3 but a negative correlation with ANGPTL4 and ANGPTL8. The results did not indicate a significant correlation among ANGPTL3, 4, and 8 levels. Thus, it is possible that the distribution of these proteins differs among patients. When patients were divided into groups according to the levels of ANGPTL3 and ANGPTL8, those with high levels of both ANGPTL3 and ANGPTL8 also had high levels of TG and small dense LDL-C/LDL-C (%). Multiple regression analysis indicated that low LPL, high ApoC2, high ApoC3, high ApoE, and high ANGPTL8 levels were the determinants of fasting hypertriglyceridemia. By contrast, no clear association was observed between any of the ANGPTLs and glucose metabolism markers, but ANGPTL8 levels were positively correlated with the levels of HOMA2-IR and BMI. Patients with high levels of both ANGPTL3 and ANGPTL8 had the worst lipid profiles. Among ANGPTL3, 4, and 8, ANGPTL8 is more important as a factor determining plasma TG levels. We anticipate that the results of this research will facilitate potential treatments targeting ANGPTL8 in patients with diabetes.

Characterization of two lipid metabolism-associated genes and their expression profiles under different feeding conditions in Acipenser dabryanus

Acipenser dabryanus is an endemic species restricted to the upper reaches of the Yangtze River and is listed as a national first-class protected animal in China. In the present study, two lipid metabolism-associated genes, namely, lipoprotein lipase (LPL) and apolipoprotein E (apoE), were identified from the full-length transcriptome analysis of A. dabryanus. The full-length genes encoded polypeptides with typical conserved motifs and functional sites shared with their homologues in other fish. Gene expression profile analysis showed that the LPL and apoE genes were constitutively expressed in A. dabryanus. The highest expression level of LPL was found in the muscle, while apoE was predominantly expressed in the liver. In the fasting and refeeding experiment, one hundred twenty fish were randomly assigned to four groups (fasting 0, 3, 7 or 14 d and then refed for 14 d). Fasting and refeeding significantly regulated the expression level of LPL with various expression patterns in different tissues, whereas starvation showed little effect on apoE expression. In addition, the expression levels of LPL and apoE were significantly affected by feeding frequency. The fish were bred for eight weeks at six different feeding frequencies groups (once a day, two times a day, three times a day, four times a day, five times a day and six times a day). Both LPL and apoE expression levels were significantly upregulated in the liver in the highest feeding frequency group. Our study suggests potential roles for LPL and apoE in lipid metabolism in A. dabryanus and will be useful for further study of nutrition regulation in fish.

Konjac Glucomannan Attenuated Triglyceride Metabolism during Rice Gruel Tolerance Test.

In a recent study, we showed that konjac glucomannan (KGM) inhibits rice gruel-induced postprandial increases in plasma glucose and insulin levels. To extend this research, we investigated the effects of KGM addition to rice gruel on pre- and postprandial concentrations of circulating lipoprotein lipase (LPL), glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), hepatic triglyceride lipase (HTGL), free fatty acids (FFA), and triglycerides (TG). A total of 13 Japanese men, without diabetes, dyslipidemia, or gastrointestinal diseases, interchangeably ingested rice gruel containing no KGM (0%G), rice gruel supplemented with 0.4% KGM (0.4%G), and rice gruel supplemented with 0.8% KGM (0.8%G), every Sunday for 3 weeks. Blood samples were obtained at baseline and at 30, 60, and 120 min after ingestion to measure the abovementioned lipid parameters. Lipid parameters showed small, but significant, changes. Significant reductions were found in circulating FFA levels among all participants. Circulating TG levels significantly declined at 30 min and then remained nearly constant in the 0.8%G group but exhibited no significant difference in the 0%G and 0.4%G groups. Although circulating levels of LPL and GPIHBP1 significantly decreased in the 0%G and 0.4%G groups, they increased at 120 min in the 0.8%G group. Participants in the 0%G and 0.4%G groups showed significant decreases in circulating HTGL levels, which was not observed in the 0.8%G group. Our results demonstrate the novel pleiotropic effects of KGM. Supplementation of rice gruel with KGM powder led to TG reduction accompanied by LPL and GPIHBP1 elevation and HTGL stabilization, thereby attenuating TG metabolism.

Impact of Dietary Crude Protein Level on Hepatic Lipid Metabolism in Weaned Female Piglets.

Simple SummaryIt has been reported that a high crude protein diet could reverse the diet-induced lipid accumulation in the liver of mice and rodents. However, in vivo data supporting a functional role of a high crude protein diet on hepatic lipid metabolism-associated genes and proteins in weaned piglets is not available. In the present study, we aimed to provide a mechanistic insight into alterations in the hepatic lipid lipogenesis, lipolysis, oxidation, and gluconeogenesis in response to different dietary crude protein levels. Our results demonstrated that dietary crude protein could regulate hepatic lipid metabolism through regulating hepatic lipid lipogenesis, lipolysis, oxidation, and gluconeogenesis. The result indicated an important role of dietary crude protein in regulating hepatic lipid metabolism in weaned piglets.Amino acids serve not only as building blocks for proteins, but also as substrates for the synthesis of low-molecular-weight substances involved in hepatic lipid metabolism. In the present study, eighteen weaned female piglets at 35 days of age were fed a corn- and soybean meal-based diet containing 20%, 17%, or 14% crude protein (CP), respectively. We found that 17% or 20% CP administration reduced the triglyceride and cholesterol concentrations, while enhanced high-density lipoprotein cholesterol (HDL-C) concentration in serum. Western blot analysis showed that piglets in the 20% CP group had higher protein abundance of hormone-sensitive triglyceride lipase (HSL) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), as compared with other groups. Moreover, the mRNA expression of sterol regulatory element binding transcription factor 1 (SREBPF1), fatty acid synthase (FASN), and stearoyl-CoA desaturase (SCD) were lower in the 17% or 20% CP group, compared with those of the piglets administered with 14% CP. Of note, the mRNA level of acetyl-CoA carboxylase alpha (ACACα) was lower in the 17% CP group, compared with other groups. Additionally, the mRNA level of lipoprotein lipase (LPL), peroxisome proliferator-activated receptor alpha α (PPARα), glucose-6-phosphatase catalytic subunit (G6PC), and phosphoenolpyruvate carboxykinase 1 (PKC1) in the liver of piglets in the 20% CP group were higher than those of the 14% CP group. Collectively, our results demonstrated that dietary CP could regulate hepatic lipid metabolism through altering hepatic lipid lipogenesis, lipolysis, oxidation, and gluconeogenesis.

DAPAGLIFLOZIN, PIOGLITAZONE AND THEIR COMBINATION EFFECTED LEVELS OF LIPOPROTEINS AND ADIPOKINES IN PLASMA AND THEIR GENE EXPRESSION IN FAT IN RATS WITH DIABETES MELLITUS TYPE 1

Objective: Patients with diabetes mellitus type1 (DM1) have a relative insulin deficiency with elevated triacylglycerides (TAG) production. Adipokines are important in fat distribution, inflammation, and endothelial function. Dapagliflozin (Dapa) and pioglitazone (Pio) are oral hypoglycemic drugs for the treatment of DM2. They have also pleiotropic effects on lipid profile and body weight. The effect of these drugs on lipoproteins and adipokines levels in DM1 is poorly understood. Design and method: DM1 in male Wistar rats was induced by a single dose of streptozotocin (STZ). Animals were then divided into five groups: Controls, diabetic animals (DM), DM treated with Dapa, DM treated with Pio, DM treated with combination DapaPio. Therapies were mixed in rat chow. Control and DM groups received standard chow. After 6 weeks of treatment serum glucose and lipid levels were determined. Visceral adipose tissue (VAT) gene expression of leptin (Lep), adiponectin (AdipoQ), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL), tumor necrosis factor-alpha (TNFa) and interleukin 6 (IL6) were measured by RT qPCR and their levels in plasma were determined by ELISA method. Results: STZ injection led to a significant increase in both fasting and postprandial glucose levels and all levels of lipoproteins except high-density lipoproteins (HDL), which were decreased. We also found decreased levels of Lep, AdipoQ, LPL, and IL6, and increased HSL and TNFa in plasma in DM group. These results were supported by the same significant changes in gene expression in VAT. A combination of DapaPio resulted in a significant decrease in serum levels of both glucose levels. Pio and DapaPio administration decreased TAG and total cholesterol and increased HDL. Lep, AdipoQ, LPL and IL6 plasma levels were increased, and HSL, TNFa were decreased after administration of Dapa, Pio and their combination. Both monotherapy and combination significantly modulated Lep, TNFa and IL6 gene expression in VAT. Conclusions: DM1 in rats influenced not only glucose levels but also lipoproteins and adipokines in plasma, which could be affected by Dapa, Pio and DapaPio. Therapy can also change the gene expression of Lep, AdipoQ, TNFa, and IL6 in adipose tissue in rats with DM1.

Effects of dietary sodium butyrate on growth, digestive enzymes, body composition and nutrient retention-related gene expression of juvenile yellow catfish (Pelteobagrus fulvidraco).

An 8-week feeding trial was conducted to evaluate the effects of sodium butyrate (SB) on growth, digestive enzymes, body composition and nutrient retention-related gene expression of juvenile yellow catfish (Pelteobagrus fulvidraco). Five isonitrogenous and isolipidic diets (420 g/kg protein and 90 g/kg lipid) were formulated to contain 0 (control), 250, 500, 1,000 or 2,000 mg/kg SB. Triplicate groups of 40 fish (BW = 1.26 ± 0.01 g) per tank (300-L cylindrical fiberglass tanks) for each diet were fed to apparent satiation twice daily. Stomach, hepatopancreas and intestine samples were obtained for digestive enzymes activities analyses. A real-time quantitative PCR analysis was performed to determine the relative expression of target of rapamycin (TOR) and lipoprotein lipase (LPL) in the hepatopancreas and intestine. Fish fed the diets supplemented with SB at 500 and 1,000 mg/kg showed significantly higher specific growth rate and significantly lower feed conversion ratio compared to the control (P < 0.05). Dietary SB inclusion did not alter activities of intestinal amylase, creatine kinase and sodium–potassium adenosine triphosphatase (Na+/K+-ATPase), but increased activities of hepatic trypsin, stomachic lipase, intestinal lipase, alkaline phosphatase and γ-glutamyl transpeptidase for fish fed 1,000 mg/kg SB compared to the control (P < 0.05). Intestine length index, intestine somatic index, fold height and muscular thickness of distal intestine were significantly higher in 1,000 mg/kg SB groups compared to the control (P < 0.05). Significantly higher levels of whole-body crude protein, ash, calcium, phosphorus, nutrition retention and relative mRNA of intestinal TOR were observed in 1,000 mg/kg SB group (P < 0.05). Whole-body lipid content and hepatopancreas LPL mRNA expression in 2,000 mg/kg SB group were significantly higher than the control (P < 0.05). Relative mRNA levels of intestinal LPL and hepatopancreas TOR were significantly higher in the 500 mg/kg SB group compared to those in other groups (P < 0.05). The increased growth performance, digestive enzymes and nutrient retention in fish fed the diets supplemented with SB at 500 and 1,000 mg/kg suggests that SB can be a desirable growth promoter as an antibiotic alternative in diets.

An evaluation on betaine and trimethylammonium hydrochloride in the diet of Carassius auratus: Growth, immunity, and fat metabolism gene expression

A 6-week feeding trial was conducted to evaluate the effects of betaine power (B-30) and trimethylammonium hydrochloride (T-98) in practical diet on growth performance, immunity, and fat metabolism gene expression of Carassius auratus (initial body weight: 3.37 ± 0.03 g). Control group was fed the basal diet, while four other groups were fed the basal diet supplemented with 1.4 g/kg B-30 (L-B group), 2.8 g/kg B-30 (H-B group), 0.5 g/kg T-98 (L-T group), and 1.0 g/kg T-98 (H-T group). The results revealed a significant improvement in specific growth rates, feed conversion ratio, and weight gain rate with L-B and L-T groups compared to control group, as well as digestive enzyme activity (lipase, amylase and protease) and immunoenzyme activity (acid phosphatase, alkaline phosphatase, lysozyme, catalase from micrococcus lysodeikticu, total antioxidant capacity, and superoxide dismutase) (P < 0.05). Futhermore, the gene expression levels of lipoprotein lipase and liver lipase in L-B and L-T groups were significantly increased compared with the control group, while the gene expression levels of fatty acid synthase were significantly decreased (P < 0.05). These data suggested that supplementation of 1.4 g/kg betaine or 0.5 g/kg trimethylammonium hydrochloride can improve the growth performence, digestive capacity, immunity, and fat metabolism gene expression of C. auratus.

The vitamin E long-chain metabolite α-13′-COOH affects macrophage foam cell formation via modulation of the lipoprotein lipase system

The α-tocopherol-derived long-chain metabolite (α-LCM) α-13′-carboxychromanol (α-13′-COOH) is formed via enzymatic degradation of α-tocopherol (α-TOH) in the liver. In the last decade, α-13′-COOH has emerged as a new regulatory metabolite revealing more potent or even different effects compared with its vitamin precursor α-TOH. The detection of α-13′-COOH in human serum has further strengthened the concept of its physiological relevance as a potential regulatory molecule. Here, we present a new facet on the interaction of α-13′-COOH with macrophage foam cell formation. We found that α-13′-COOH (5 μM) increases angiopoietin-like 4 (ANGPTL4) mRNA expression in human THP-1 macrophages in a time- and dose-dependent manner, while α-TOH (100 μM) showed no effects. Interestingly, the mRNA level of lipoprotein lipase (LPL) was not influenced by α-13′-COOH, but α-TOH treatment led to a reduction of LPL mRNA expression. Both compounds also revealed different effects on protein level: while α-13′-COOH reduced the secreted amount of LPL protein via induction of ANGPTL4 cleavage, i.e. activation, the secreted amount of LPL in the α-TOH-treated samples was diminished due to the inhibition of mRNA expression. In line with this, both compounds reduced the catalytic activity of LPL. However, α-13′-COOH but not α-TOH attenuated VLDL-induced lipid accumulation by 35%. In conclusion, only α-13′-COOH revealed possible antiatherogenic effects due to the reduction of VLDL-induced foam cell formation in THP-1 macrophages. Our results provide further evidence for the role of α-13′-COOH as a functional metabolite of its vitamin E precursor.

Association of lipoprotein lipase expression with TP53 gene polymorphisms in chronic lymphocytic leukemia cells.

Expression of lipoprotein lipase (LPL) correlates with unmutated (UM) status of the variable region of the heavy chain of immunoglobulin (IGHV) genes, but the expression level of LPL in UM chronic lymphocytic leukemia (CLL) cases varies significantly. To study the association of LPL expression with the genetic variants of the TP53gene since both genes are involved in lipid metabolism. Expression of LPL mRNA was measured in peripheral blood mononuclears of 45CLL patients with UM IGHV genes by real-time quantitative reverse transcription polymerase chain reaction. Mutational status of IGHV genes and TP53genotyping (rs1042522, rs1642785, rs17883323, rs2909430, rs145153611, rs113530090, rs12947788, rs12951053, and rs17878362) were performed by polymerase chain reaction amplification followed by direct sequencing. Observed CLL patients were divided on groups with low (11.17 ± 2.66) and high (275.48 ± 39.37) LPL expression. In CLL patients with UM IGHV genes and low LPL expression we found an increased frequency of rs1042522G (p= 0.0036), rs1642785C (p= 0.0001), and rs17878362A2alleles (p= 0.0091). The possible functional significance of these changes is discussed. Some polymorphic variants of TP53may be genetic modifiers for LPL expression level in CLL leukemic B-cells. Further research is required in a larger cohort to confirm these findings.

Decreased Triglyceride and Increased Serum Lipoprotein Lipase Levels Are Correlated to Increased High-Density Lipoprotein-Cholesterol Levels after Laparoscopic Sleeve Gastrectomy

Introduction: Laparoscopic sleeve gastrectomy (LSG) significantly increases high-density lipoprotein cholesterol (HDL-C) and lipoprotein lipase (LPL) in pre-heparin serum (pre-heparin LPL levels). LPL is a regulator of serum triglyceride (TG) and HDL-C production; this may be the mechanism for HDL-C increase after LSG. This study aimed to elucidate the mechanism of increase in HDL-C levels by examining the relationship between changes in serum HDL-C levels and LPL after LSG. Methods: We retrospectively reviewed 104 obese patients, who underwent LSG and were followed up for 12 months. We analyzed the relationship between changes in serum HDL-C levels and various clinical parameters after LSG. Results: A significant decrease was observed in the patients’ BMI and serum TG levels after LSG. Conversely, HDL-C levels and pre-heparin LPL levels were significantly increased after LSG. Simple linear regression showed that changes in HDL-C levels were significantly correlated with total weight loss percentage, change in TG levels, abdominal fat areas, and pre-heparin LPL levels. Additionally, the multiple regression model revealed that a decrease in TG levels and an increase in pre-heparin LPL levels were correlated with increased HDL-C levels after LSG. Discussion/Conclusion: These results show that a decrease in TG levels and an increase in LPL are mechanisms for increased HDL-C levels after LSG.

Assessment of Adipocyte Differentiation and Maturation-related Gene Expression in the Epididymal Fat of Estrogen Receptor α Knockout (ERαKO) Mouse during Postnatal Development Period.

The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. The present research was aimed to evaluate expression of various molecules associated with adipocyte differentiation and maturation in the epididymal fat of ERαKO mouse at several postnatal ages by using quantitative real-time polymerase chain reaction. The highest transcript levels of all molecules were detected at 12 months of postnatal age, except leptin which the mRNA level was increased at 5 months of age and was unchanged until 12 months of age. The expression levels of CCAAT enhancer binding protein (Cebp) alpha, androgen receptor, and lipoprotein lipase were decreased at 5 months of age but increased at about 8 months of age. The mRNA levels of Cebp gamma and sterol regulatory element binding transcription factor 1 remained steady until 8 months of age. Continuous increases of transcript levels during postnatal period were found in Cebp beta, estrogen receptor (ER) beta, fatty acid binding protein 4, and delta like non-canonical Notch ligand 1. The increases of peroxisome proliferator-activated receptor gamma and adiponectin mRNA levels were detected as early as 8 months of age. The levels of fatty acid synthase and resistin transcript at 5 and 8 months of age were lower than that at 2 months of age. These findings show the aberrant expression patterns of genes related to adipocyte differentiation and maturation in the postnatal epididymal fat pad by the disruption of ER alpha function.

Maslinic acid and gallic acid protective efficacy on lipids, lipoproteins and lipid metabolizing enzymes against isoproterenol administered cardiotoxicity: An in vivo and in silico molecular docking evidences

ObjectiveThe current study designed to investigate the protective efficacy of maslinic acid (MA) and gallic acid (GA) against isoproterenol (ISO) administered cardiac toxicity in rats by exploring in vivo and in silico approaches. MethodsThe animals were divided into five different groups. The individual animal groups were orally pretreated with MA (15 mg/kg) and GA ((15 mg/kg) for 7 days and ISO administered subcutaneously on 8th and 9th days to induce MI. Blood, heart and liver were collected from sacrificed animals and used for biochemical analysis. ResultsThe results represented significant decrease in the levels of high density lipoprotein cholesterol, lipoprotein lipase and lecithin cholesterol acyl transferase whereas significant increase in the levels of total cholesterol, triglycerides, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and HMG-CoA reductase in ISO (85 mg/kg) treated rats. However, pretreatment of ISO treated rats with MA and GA markedly brought all the parameters such as lipids, lipoproteins and lipid metabolic marker enzymes to near normal level indicating the ameliorating effect of MA and GA against MI. Further, the investigation extended to in silico analysis to study the interaction of MA and GA with the key lipid metabolizing enzymes by using Gold 3.0.1 software. The molecular docking studies revealed that HMG-CoA reductase, LPL and LCAT formed strong enzyme ligand complexes with MA and GA. ConclusionsMA and GA exhibited protective efficacy against ISO administered cardiotoxicity and the results further supported by molecular docking studies.

Adipose extracellular signal-regulated kinase 2 protected from endothelial dysfunction and the oxidative stress of perivascular adipose tissue in obese mice

Abstract Introduction Extracellular signal-regulated kinase (ERK) modulates differentiation and maturation of adipocyte and the hypertrophy and differentiation of adipocytes affected the vascular diseases in obese. Changes in characters of adipocytes could develope the oxidative stress and inflammations. Moreover, changes in perivascular adipose tissue (PVAT) could modulate vascular tonus in obesity. However, the role of adipose ERK2 in endothelial function and characters of PVAT in obese in vivo had not been clarified, yet. Purpose This study aims to elucidate the role of the adipose ERK2 in endothelial-dependent relaxation (EDR) in mice model of obesity. The role of PVAT in EDR was also assessed. Methods and results We created adipose-specific ERK2 knock out mice (AE2KO) by crossing fatty acid binding protein 4 Cre and ERK2 flox mice and fed them with normal diet (ND) or high fat/ high sucrose diet (HFHSD) for 24 weeks. AE2KO fed with HFHSD gained more weight and revealed the heterogeneity in sizes of adipocyte in subcutaneous fat (SF). Furthermore, the mRNA levels of lipoprotein lipase, hormone-sensitive lipase, and peroxisome proliferator-activated receptor γ, which was the master genes of adipocyte differentiation, were markedly down-regulated in SF. PVAT in AE2KO with HFHSD was markedly enlarged and the mRNA expression of inflammatory adipocytokines, such as IL-1β and leptin were up-regulated. Next, we assessed EDR by acetylcholine (ACh) -induced relaxation in aortic rings with or without PVAT. EDR without PVAT was modestly decreased in AE2KO with HFHSD compared with wild type mice (WT) with HFHSD. Aortic rings with PVAT increased EDR in WT with ND. PVAT modestly decreased EDR in WT with HFHSD and mostly eliminated EDR in AE2KO with HFHSD. To assess the contraction factors released from PVAT, the solutions incubated with PVAT (SIP) were transferred to the normal aortic rings. SIP from WT with HFHSD mildly increased vascular tone and SIP from AE2KO with HFHSD further increased it. Tempol, which was superoxide scavenger, restored endothelial dysfunction with PVAT and suppressed the contraction with SIP from AE2KO with HFHSD. Fluorescence intensity of dihydroethidium stain of aorta and PVAT, which indicated that aortic and adipose superoxide production were elevated in AE2KO with HFHSD, which were mostly eliminated with tempol. Conclusions Adipose ERK2 selectively modulated differentiation in SF, suppressed the aortic oxidative stress and protected from endothelial dysfunction in obese. Moreover, adipose ERK2 suppressed the hypertrophy, inflammation, and oxidative stress of PVAT in obese. The oxidative stress with the inflammation in PVAT released vasoconstriction factors, which contributed to endothelial dysfunction in obese mice. Figure 1 Funding Acknowledgement Type of funding source: None

Association of LPL Gene Variant and Serum LPL Level with Ischemic Stroke in Iraqi Population

Background: Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism.An increasing number of studies have suggested an association of LPL gene variants with the risk ofcardiovascular and cerebrovascular diseases.Objective: To analyze whether Hind III polymorphism of LPL gene and serum LPL level are associatedwith ischemic stroke in Iraqi population.Method: Fifty ischemic stroke patients (clinical diagnosis and x-ray CT) and fifty controls were enrolled inthis case–control study. The LPL Hind III polymorphism was determined by PCR-RFLP technique and LPLmass level was estimated using a sensitive sandwich enzyme-linked immunosorbent assay (ELISA).Results: In the present research was not found any association between the Hindlll LPL gene polymorphismand acute ischemic stroke in the population studied; the allele and genotypic frequencies of the studiedpolymorphism was similar in cases and controls and followed the Hardy-Weinberg equilibrium. Therelationship between Hind III genotypes and the LPL mass level was analyzed using ANOVA and furtherconfirmed by Post-hoc analysis. there was no significant difference in LPL mass levels between the genotypegroups H+H+, H+H-, and H-H- (p value&gt;0.05).Conclusions: The Hind III polymorphism of LPLis not a genetic marker for the development of ischemicstroke as well as not determinants of serum LPL level in the Iraqian sample used.

Effect of maternal nutrient restriction on expression of glucose transporters (SLC2A4 and SLC2A1) and insulin signaling in skeletal muscle of SGA and Non-SGA sheep fetuses

Maternal nutrient restriction (NR) causes small for gestational age (SGA) offspring, which are at higher risk for accelerated postnatal growth and developing insulin resistance in adulthood. Skeletal muscle is essential for whole-body glucose metabolism, as 80% of insulin-mediated glucose uptake occurs in this tissue. Maternal NR can alter fetal skeletal muscle mass, expression of glucose transporters, insulin signaling, and myofiber type composition. It also leads to accumulation of intramuscular triglycerides (IMTG), which correlates to insulin resistance. Using a 50% NR treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the NR group. Thus, we classified those fetuses into NR(Non-SGA; n = 11) and NR(SGA; n = 11). The control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and gastrocnemius and soleus muscles were collected. In fetal plasma, total insulin was lower in NR(SGA) fetuses compared NR(Non-SGA) and control fetuses (P < 0.01), whereas total IGF-1 was lower in NR(SGA) fetuses compared with control fetuses (P < 0.05). Within gastrocnemius, protein expression of insulin receptor (INSRB; P < 0.05) and the glucose transporters, solute carrier family 2 member 1 and solute carrier family 2 member 4, was higher (P < 0.05) in NR(SGA) fetuses compared with NR(Non-SGA) fetuses; IGF-1 receptor protein was increased (P < 0.01) in NR(SGA) fetuses compared with control fetuses, and a lower (P < 0.01) proportion of type I myofibers (insulin sensitive and oxidative) was observed in SGA fetuses. For gastrocnemius muscle, the expression of lipoprotein lipase (LPL) messenger RNA (mRNA) was upregulated (P < 0.05) in both NR(SGA) and NR(Non-SGA) fetuses compared with control fetuses, whereas carnitine palmitoyltransferase 1B (CPT1B) mRNA was higher (P < 0.05) in NR(Non-SGA) fetuses compared with control fetuses, but there were no differences (P > 0.05) for protein levels of LPL or CPT1B. Within soleus, there were no differences (P > 0.05) for any characteristic except for the proportion of type I myofibers, which was lower (P < 0.05) in NR(SGA) fetuses compared with control fetuses. Accumulation of IMTG did not differ (P > 0.05) in gastrocnemius or soleus muscles. Collectively, the results indicate molecular differences between SGA and Non-SGA fetuses for most characteristics, suggesting that maternal NR induces a spectral phenotype for the metabolic programming of those fetuses.

Key metabolic and enzymatic adaptations underlie the benefits of formulated diets in the adult female Chinese mitten crabEriocheir sinensis

Natural and traditional diets have been gradually replaced with formulated diets for the Chinese mitten crab Eriocheir sinensis culture, but it is unclear what effects different feeding modes have on digestive physiology and metabolism of E. sinensis. This study investigated the effects of three feeding modes, formulated diets (FD), natural diets (ND, trash fish and freshwater snails) and traditional diets (TD, soybean, wheat, broad bean and corn) on digestive enzyme activity, physiological indices and metabolomics of adult female E. sinensis. The ND had the highest activities of trypsin and lipase in the hepatopancreas, while the highest amylase activity was detected in TD. The highest content of hepatopancreas triglyceride was detected in FD, while the highest levels of lipoprotein lipase, hepatic lipase, lactic acid, malonaldehyde, acid phosphatase and alkaline phosphatase in the hepatopancreas, as well as the total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and γ-glutamyltransferase in serum were detected in ND. The TD had the highest content of glucose and uric acid in the hepatopancreas as well as the free cholesterol, lactic acid, aspartate aminotransferase and alanine aminotransferase in the serum. The metabolomics showed that most differential metabolites involved in amino acid anabolism in serum and hepatopancreas were significantly up-regulated in FD. The metabolites involved in energy metabolism and gluconeogenesis in the hepatopancreas were significantly down-regulated in FD. These results suggested that feeding with formulated diets promotes amino acid synthesis and reduces energy metabolism, which leads to more protein and glucose deposition in tissue.

The antagonic behavior of GPIHBP1 between EAT and circulation does not reflect lipolytic enzymes levels in the tissue and serum from coronary patients

BackgroundCoronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Recently, triglyceride rich lipoproteins are proposed to contribute to CAD risk; its concentrations would be partly determined by lipoprotein lipase (LPL) and endothelial lipase (EL). Epicardial adipose tissue (EAT), a visceral AT surrounding myocardium and coronary arteries, emerged as an important actor in CAD; the increase in its volume could be a consequence of LPL and EL. Circulating enzymes levels would be conditioned by local tissue factors. Our aim was to evaluate LPL, EL and their regulators levels in serum and EAT from CAD patients, searching for possible parallelisms and their role in the lipoprotein profile. MethodsIn serum, EAT and subcutaneous AT (SAT) from patients undergoing coronary artery bypass graft (CABG, n = 25) or valve replacement (No CABG, n = 25), LPL, EL and glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein-1 (GPIHBP1) expression were evaluated. Besides, Apoprotein (Apo)CII, CIII and AV were determined in serum, along with lipoprotein profile. ResultsInsulin-resistance markers were higher in CABG (p < 0.05). Serum LPL levels were decreased (p = 0.045), while EL levels increased (p < 0.001) in CABG, without differences in EAT or SAT. Circulating GPIHBP1 concentrations were decreased in CABG (p = 0.047), while EAT GPIHBP1 expression was increased (p < 0.001). ApoCII and ApoAV concentrations were higher in CABG (p = 0.016 and p = 0.047, respectively), without differences in ApoCIII concentrations between groups. ConclusionsIn EAT, LPL and EL protein levels were not changed in CAD, although GPIHBP1 protein levels were higher. EAT would be a minor contributor to the circulating levels of the enzymes.

Association Between BMP2 Functional Polymorphisms and Sheep Tail Type.

Simple SummaryWe previously detected selection markers of sheep with different tail types and found that bone morphogenetic protein 2 (BMP2) was strongly selected. We therefore predicted that BMP2 might be involved in fat deposition in sheep tails or related to sheep tail type. However, no studies have investigated the molecular mechanism of BMP2 in the formation of sheep tails. In this study, we performed flight mass spectrometry genotyping on the BMP2 gene of 533 sheep with different tail types and functionally verified our results at the cellular level. This aimed to provide basic research data for the regulation of fat deposition in sheep tails and to identify genetic markers for molecular breeding.Bone morphogenetic protein 2 (BMP2) is strongly selected in both fat-tailed and thin-tailed sheep and may be a candidate gene for sheep tail type selection. However, the mechanism of action of BMP2 in sheep tail fat deposition remains unclear. This study investigated genetic variation and haplotype combinations of the BMP2 gene in sheep with different tail types, aiming to reveal the molecular mechanism of BMP2 in sheep tail fat deposition. We detected a total of three single nucleotide polymorphisms (SNPs) (g.48401619 T > A, g.48401272 C > A, and g.48401136 C > T) among 533 sheep. The alleles and genotype frequencies of these SNPs were in Hardy–Weinberg equilibrium and showed significant correlations with tail length. Linkage disequilibrium existed between the g.48401272 C > A and g.48401136 C > T sites, where CACT was the predominant genotype. At the cellular level, the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) were upregulated after BMP2 overexpression; there were significantly higher levels of PPARγ than controls at 0 d and 1 d, and of LPL than controls at 1 d and 7 d. These results indicate that the BMP2 gene may participate in sheep tail fat deposition and could be used for molecular-marker-assisted selection of sheep tail type.

The influence of equine body weight gain on inflammatory cytokine expressions of adipose tissue in response to endotoxin challenge

BackgroundHuman obesity is linked with systemic inflammation. However, it is still controversial if equines produce more inflammatory cytokines with increasing body weight and if the production of those show breed type specific patterns. The main objective of this study was to determine if diet induced obesity is associated with increased inflammatory signatures in adipose tissue of equines and if a breed predisposition exists between ponies and horses. Additionally, we aimed to identify adipose tissue depot differences in inflammatory cytokine expression. Nineteen healthy, non-overweight and metabolically healthy equines received a hypercaloric diet for 2 years. Body weight, body condition score and cresty neck score were assessed weekly throughout the study. At three time points, insulin sensitivity was determined by a combined glucose-insulin test. Adipose tissue samples were collected from two intra-abdominal and two subcutaneous depots under general anesthesia at each time point after an endotoxin trigger. In the adipose tissue samples levels of CD68 mRNA (a marker of macrophage infiltration) and pro-inflammatory cytokine mRNA (IL-1β, IL-6 and TNFα) were analyzed with RT-qPCR. As markers of lipid metabolism mRNA levels of lipoprotein lipase (LPL) and fatty acid binding protein 4 (FABP4) were determined with RT-qPCR.ResultsCD68 mRNA levels increased with body weight gain in several adipose tissue (AT) depots (Wilcoxon signed rank test with Bonferroni correction; retroperitoneal AT horses: P = 0.023, mesocolonial AT horses: P = 0.023, subcutaneous tail head AT ponies: P = 0.015). In both abdominal depots CD68 mRNA levels were higher than in subcutaneous adipose tissue depots (Kruskal–Wallis-ANOVA with Bonferroni correction: P < 0.05). No breed related differences were found. Pro-inflammatory cytokine mRNA IL-1β, IL-6 and TNFα levels were higher in subcutaneous depots compared to abdominal depots after body weight gain. IL-1β, IL-6 and TNFα mRNA levels of mesocolon adipose tissue were higher in obese horses compared to obese ponies (Mann–Whitney-U test; IL-1β: P = 0.006; IL-6: P = 0.003; TNFα: P = 0.049). In general, horses had higher FABP4 and LPL mRNA levels compared to ponies in neck AT and tail AT at all time points.ConclusionOur findings suggest an increased invasion of macrophages in intra-abdominal adipose tissue with increasing body weight gain in equines in combination with a low dose endotoxin stimulus. This might predispose equines to obesity related comorbidities. In obese horses mesocolon adipose tissue showed higher inflammatory cytokine expression compared to obese ponies. Additionally, subcutaneous adipose tissue expressed more pro-inflammatory cytokines compared to intra-abdominal adipose tissue. Horses had higher FABP4 and LPL mRNA levels in selected AT depots which may indicate a higher fat storage capacity than in ponies. The differences in lipid storage might be associated with a higher susceptibility to obesity-related comorbidities in ponies in comparison to horses.