Correlation between betatrophin/angiogenin-likeprotein3/lipoprotein lipase pathway and severity of coronary artery disease in Kazakh patients with coronary heart disease

BACKGROUND The results of previous animal experiments and clinical studies have shown that there is a correlation between expression of betatrophin and blood lipid levels.However,there are still differences studies on the correlation and interaction mechanism between betatrophin,angiogenin-likeprotein3(ANGPTL3)and lipoprotein lipase(LPL).In our previous studies,we found an increase in serum ANGPTL3 Levels in Chinese patients with coronary heart disease(CHD).Therefore,we retrospectively studied Kazakh CHD patients.AIM To explore the correlation between the betatrophin/ANGPTL3/LPL pathway and severity of coronary artery disease(CAD)in patients with CHD.METHODS Nondiabetic patients diagnosed with CHD were selected as the case group;79 were of Kazakh descent and 72 were of Han descent.The control groups comprised of 61 Kazakh and 65 Han individuals.The serum levels of betatrophin and LPL were detected by enzyme-linked immunosorbent assay(ELISA),and the double antibody sandwich ELISA was used to detect serum level of ANGPTL3.The levels of triglycerides,total cholesterol,and fasting blood glucose in each group were determined by an automatic biochemical analyzer.At the same time,the clinical baseline data of patients in each group were included.RESULTS Betatrophin,ANGPTL3 and LPL levels of Kazakh patients were significantly higher than those of Han patients(P=0.031,0.038,0.021 respectively).There was a positive correlation between the Gensini score and total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),betatrophin,and LPL in Kazakh patients(r=0.204,0.453,0.352,0.471,and 0.382 respectively),(P=0.043,0.009,0.048,0.001,and P<0.001 respectively).A positive correlation was found between the Gensini score and body mass index(BMI),TC,TG,LDL-C,LPL,betatrophin in Han patients(r=0.438,0.195,0.296,0.357,0.328,and 0.446 respectively),(P=0.044,0.026,0.003,0.20,0.004,and P<0.001).TG and betatrophin were the risk factors of coronary artery disease in Kazakh patients,while BMI and betatrophin were the risk factors in Han patients.CONCLUSION There was a correlation between the betatrophin/ANGPTL3/LPL pathway and severity of CAD in patients with CHD.

Effect of Lipoprotein Lipase Gene Polymorphism on Plasma Lipid Levels, BMI and Subcutaneous Fat Distribution in Simple Obesity Children

Objective To study the effects of Hind Ⅲ DNA polymorphism in the lipoprotein lipase (LPL)gene on plasma lipid levels, body mass index (BMI) and subcutaneous fat distribution in simple obesity children.Methods The LPL Hind Ⅲ genotypes were detected with the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in 92 children with simple obesity. The levels of the plasma lipid, plasma lipoproteins, BMI and skinfold thickness in three regions (biceps, subscapular and abdominal wall) were also measured. Results It was shown that the levels of TG, TC, LDL C, ApoB, BMI, biceps and subscapular skinfold thickness, and the average value of the skinfold thickness in three regions were significantly higher in the obese children with H+H+ genotype than those with H+H-genotype. Conclusions It can be concluded that LPL Hind Ⅲ polymorphism may modify the levels of plasma lipid, plasma lipoprotein and BMI in children with simple obesity, and meanwhile alters the distribution of subcutaneous fat.

Knockout of lipoprotein lipase with CRISPR/Cas9 causes severe developmental defects and affects lipid deposition in Japanese medaka(Oryzias latipes)

In mammals,lipoprotein lipase(LPL)has been found to play an important role in lipid mentalismand deposition.LPL deficiency in humans(Homo sapiens)and mice(Mus musculus)tends to cause hypertriglyceridemia.The lpl gene is not expressed in adult mammalian liver,but is in adult fish liver.The functions provided by the lpl gene are diverse in vertebrates.Here,we knocked out the lpl gene in Japanese medaka(Oryzias latipes)with the CRISPR/Cas9 system.The lpl-knockout(KO)homozygous individuals showed severe developmental defects with an extremely emaciated and deformedbody and onlyaccounted for about5%of the F2fish.This is consistentwiththefindings inmicebut disaccords with the results for zebrafish(Danio rerio).Compared with wild-type(WT)madaka,the mRNA level of lpl in lpl-KO heterozygous mutant was significantly higher in the muscle,showed no significant difference in the liver,and was significantly lower in the heart.Under lpl heterozygous deficiency,the relative area of Oil RedO and triglycerides(TG)level in the liver,heart and muscle tissue covaried with levels of lpl mRNA in medaka.The lpl heterozygous deficiency did not affect the levelsofTG,low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)and total cholesterol(TC)in the plasma of medaka,which is inconsistent with the findings in mammals.In general,the lpl gene plays an important role in the growth and development and is closely related to lipid deposition of medaka.

The interplay between non-esterified fatty acids and bovine peroxisome proliferator-activated receptors: results of an in vitro hybrid approach

Background: In dairy cows circulating non-esterified fatty acids(NEFA) increase early post-partum while liver and other tissues undergo adaptation to greater lipid metabolism, mainly regulated by peroxisome proliferator-activated receptors(PPAR). PPAR are activated by fatty acids(FA), but it remains to be demonstrated that circulating NEFA or dietary FA activate bovine PPAR. We hypothesized that circulating NEFA and dietary FA activate PPAR in dairy cows.Methods: The dose-response activation of PPAR by NEFA or dietary FA was assessed using HP300 e digital dispenser and luciferase reporter in several bovine cell types. Cells were treated with blood plasma isolated from Jersey cows before and after parturition, NEFA isolated from the blood plasma, FA released from lipoproteins using milk lipoprotein lipase(LPL), and palmitic acid(C16:0). Effect on each PPAR isotype was assessed using specific synthetic inhibitors.Results: NEFA isolated from blood serum activate PPAR linearly up to ~ 4-fold at 400 μmol/L in MAC-T cells but had cytotoxic effect. Addition of albumin to the culture media decreases cytotoxic effects of NEFA but also PPAR activation by ~ 2-fold. Treating cells with serum from peripartum cows reveals that much of the PPAR activation can be explained by the amount of NEFA in the serum(R~2 = 0.91) and that the response to serum NEFA follows a quadratic tendency, with peak activation around 1.4 mmol/L. Analysis of PPAR activation by serum in MAC-T, BFH-12 and BPAEC cells revealed that most of the activation is explained by the activity of PPARδ and PPARγ, but not PPARα. Palmitic acid activated PPAR when added in culture media or blood serum but the activation was limited to PPARδ and PPARα and the response was nil in serum from post-partum cows. The addition of LPL to the serum increased > 1.5-fold PPAR activation.Conclusion: Our results support dose-dependent activation of PPAR by circulating NEFA in bovine, specifically δand γ isotypes. Data also support the possibility of increasing PPAR activation by dietary FA;however, this nutrigenomics approach maybe only effective in pre-partum but not post-partum cows.

Rapid Decrease and Subsequent Increase in the Serum Triglycerides Accompanied by CD36 Transcript Increase in an Acute Stress Mice Model

In this article, we report the changes in serum triglyceride (TG) levels that occurred during repeated tail blood sampling using a mouse restrainer. We used three groups of mice, namely, “PBS-restrained” “PBS-unrestrained” and “mock-restrained”. The mice in the PBS-restrained and PBS-unrestrained groups were intraperitoneally (i.p.) injected with 100 mL PBS and tail blood sampling was performed at 1, 5, 8, 24, and 48 h after i.p. injection. For the mock-restrained group, no i.p. injection was performed whereas the subsequent tail blood sampling was similarly performed. During the tail blood sampling, the mice of the two “restrained” groups were placed inside the restrainer designed from an open-ended 50 mL conical tube. The blood from the mice in the PBS-unrestrained group mice was sampled from the tail held by the operator’s hands while being allowed to move on a stage. Strikingly, in all of the three groups, the serum TG level initially decreased to remarkably low levels (approximately 30 mg/dL) after several blood samplings were performed over 8 h. This decrease was followed by a 2 - 3-fold increase in the levels relative to that in the control mice in the subsequent 24 - 48 h time period. We concluded that the acute stress associated with blood sampling caused alterations in TG levels. Serum levels of free fatty acid showed only modest changes. Changes in TG levels were not associated with serum corticosterone levels but with a dramatic increase in CD36 transcript levels in the liver. The relevance of this finding to the previously reported release of lipoprotein lipase (LPL) from white fatty tissue into the plasma during acute stress is also discussed.

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(Pel-teobagrus fulvidraco).Five isonitmgenous 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 rapa-mycin(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 y-glutamyl trans-peptidase 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 gmup 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.