LDL Receptor Gene Expression Research Articles

Investigation of Cytotoxicity and Lipid-lowering Effects of Rivea hypocrateriformis Desr. Leaf Extracts on HepG2 Cells: An In Vitro Study

Background and Purpose Chronic diseases, such as cardiovascular disease as well as type 2 diabetes, are associated with hyperlipidemia, characterized by high blood lipid levels. HepG2 cells, a human liver cancer cell line, have become a popular model for evaluating the effectiveness of drugs in treating hyperlipidemia. These cells are preferred due to their ability to mimic liver cell physiology and easy maintenance in culture. Methods In this study, HEP, HEC, HEA, and HEE extracts of Rivea hypocrateriformis were tested on HepG2 cells for cytotoxicity using the MTT assay. The IC50 values of the extracts were determined and compared to analyze their toxicity. Microscopic images of the cell lines were also examined to observe any structural changes induced by the extracts. Results and Conclusion The results showed that both HEC and HEE extracts exhibited significant toxicity on HepG2 cells at the highest concentration of 500 µg/ml. Gradual decreases in concentration led to a gradual rise in % cell viability. The IC50 values of HEC and HEE were calculated to be 61.49 µg/ml and 87.08 µg/ml, respectively, indicating that HEC was slightly more toxic than HEE. According to the results obtained using the vanilla method, HEC and HEE extracts markedly reduced lipid content compared to the oleic acid-induced group. The gene expression regulation of AMPK, FAS, LDL receptor, and HMG-CoA was investigated using the RT-PCR method. The results showed that the extract-treated groups exhibited higher AMPK and LDL receptor gene expression. In contrast, the HEE extract showed higher activity than HEC in suppressing the FAS gene. Overall, the findings suggest that HEC and HEE extracts have potential as anticancer and lipid-lowering agents. Detailed research is needed to understand how the active constituents work.

Examining the expression of low-density lipoprotein receptor (LDLR) and low-density lipoprotein receptor-related protein 6 (LRP6) genes in breast cancer cell lines.

Cholesterol and the Wnt/β-catenin pathway have an effective role in the proliferation, survival, drug resistance, immune exhaustion, and metastasis of all types of cancer cells. Considering the role of LDLR and LRP6 proteins in cholesterol uptake by cells and activation of Wnt/β-catenin pathway, this study aims to examine the gene expression of LDLR and LRP6 in cell lines of breast cancer. Human breast cancer cell lines MCF7, MD468 and SKBR3 were cultured in suitable conditions and after extracting total RNA from them, real-Time PCR was used to measure the levels of gene expression for LDLR and LRP6. Our results showed that the expression of LDLR and LRP6 genes is significantly increased in MCF7 and MD468 cells compared to SKBR3 cells. These results suggest that LRP6 and LDLR can be considered as a therapeutic target in tumors that have a genetic profile similar to MCF7 and MD468 cells.

Impact of Bariatric Surgery on Subtilisin/Kexin Type 9 (PCSK9) Gene Expression and Inflammation in the Adipose Tissue of Obese Diabetic Rats.

Bariatric surgery improves dyslipidaemia and reduces body weight, but it remains unclear how bariatric surgery modulates gene expression in fat cells to influence the proprotein convertase subtilisin/kexin type 9 (PCSK-9) and low-density lipoprotein receptor (LDLR) gene expression. The expression of the PCSK9/LDLR/tumor necrosis factor-alpha (TNFα) gene in adipose tissue was measured in two groups of Zucker Diabetic Sprague Dawley (ZDSD) rats after Roux-en-Y gastric bypass (RYGB) surgery or 'SHAM' operation. There was lower PCSK9 (p = 0.02) and higher LDLR gene expression (p = 0.02) in adipose tissue in rats after RYGB. Weight change did not correlate with PCSK9 gene expression (r = -0.5, p = 0.08) or TNFα gene expression (r = -0.4, p = 0.1). TNFα gene expression was positively correlated with PCSK9 gene expression (r = 0.7, p = 0.001) but not correlated with LDLR expression (r = -0.3, p = 0.3). Circulating triglyceride levels were lower in RYGB compared to the SHAM group (1.1 (0.8-1.4) vs. 1.5 (1.0-4.2), p = 0.038) mmol/L with no difference in cholesterol levels. LDLR gene expression was increased post-bariatric surgery with the potential to reduce the number of circulating LDL particles. PCSK9 gene expression and TNFα gene expression were positively correlated after RYGB in ZDSD rats, suggesting that the modulation of pro-inflammatory pathways in adipose tissue after RYGB may partly relate to PCSK9 and LDLR gene expression.

Rhamnetin decreases the expression of HMG-CoA reductase gene and increases LDL receptor in HepG2 cells

Context: Rhamnetin is a naturally occurring methylated derivative of quercetin. This flavonoid is abundant in Syzygium aromaticum, Coriandrum sativum Prunus cerasus, and Rhamnus spp. Aims: To evaluate the effects of rhamnetin on HMG-CoA reductase and low-density lipoprotein receptor (LDLR) gene and protein expressions in the HepG2 hepatoma cell line. Methods: The expression of HMG-CoA reductase and LDLR genes and proteins were studied in HepG2 liver cancer cell line by PCR, Western blot, and indirect ELISA, as well as their antioxidant activity. Results: Rhamnetin was non-toxic up to 200 μM on HepG2 at 24, 48, and 72 h. Rhamnetin (25 µM) upregulated LDLR gene expression by 1.66 folds compared to 3.12 folds exerted by the well-known hypocholesterolemic drug simvastatin. Rhamnetin (100 µM) increased the expression of LDLR protein at the cell membrane, while the other concentrations produced no significant change from the control (vehicle-treated). In HepG2 cell lysate, LDLR was increased by 50 µM of rhamnetin. Also, rhamnetin increased SOD activity significantly by 100.98, 86.28, and 100.98% by the concentrations 25, 50, and 100 µM, respectively. Using the same concentrations, rhamnetin reduced H2O2 levels by 50, 67, and 76.34%, respectively. Conclusions: This study demonstrated for the first time that rhamnetin reduced HMG-CoA reductase gene expression and increased LDLR in HepG2 cells.

Differential cholesterol uptake in liver cells: A role for PCSK9.

The clearance of low-density lipoprotein (LDL) particles from the circulation is regulated by the LDL receptor (LDLR) and proprotein convertase subtilisin/kexin 9 (PCSK9) interaction. Its disruption reduces blood cholesterol levels and delays atherosclerosis progression. Whether other members of the LDLR superfamily are in vivo targets of PCSK9has been poorly explored. The aim of this work was to study the interaction between PCSK9 and members of the LDLR superfamily in the regulation of liver cholesterol homeostasis in an in vivo low-density lipoprotein receptor related protein 5 (LRP5) deficient mice model challenged with high-fat diet. Our results show that Wt and Lrp5-/- mice fed a hypercholesterolemic diet (HC) have increased cholesterol ester accumulation and decreased liver LDLR and LRP5gene and protein expression. Very low-density lipoprotein receptor (VLDLR), LRP6, LRP2, and LRP1 expression levels were analyzed in liver samples and show that they do not participate in Lrp5-/- liver cholesterol uptake. Immunoprecipitation experiments show that LRP5 forms a complex with PCSK9 in liver-specific fat-storing stellate cells but not in structural HepG2 cells. Hepatic stellate cells silenced for LRP5 and/or PCSK9 expression and challenged with lipids show reduced cholesterol ester accumulation, indicating that both proteins are involved in lipid processing in the liver. Our results indicate that cholesterol esters accumulate in livers of Wt mice in a LDLR-family-members dependent manner as VLDLR, LRP2, and LRP6show increased expression in HC mice. However, this increase is lost in livers of Lrp5-/- mice, where scavenger receptors are involved in cholesterol uptake. PCSK9 expression is strongly downregulated in mice livers after HC feeding. However PCSK9 and LRP5 bind in the cytoplasm of fat storing liver cells, indicating that this PCSK9-LRP5 interaction is cell-type specific and that both proteins contribute to lipid uptake.

P–658 Lovastatin promotes the expression of LDL receptor and enhances E2 production in the cumulus cells

Abstract Study question Lovastatin enhanced E2 productive ratios in the cumulus cells through promoted expression of Low-density lipoprotein receptor (LDLR). Summary answer Lovastatin up-regulated gene expression of LDLR in the CCs. And the high expression of LDLR promoted E2 productive ratios from CCs. What is known already We already reported that the up-regulation of LDLR correlated with clinical pregnancy. Therefore, we found lovastatin as an up-regulator of LDLR expression of clinical pregnancy. Study design, size, duration This is an expended study of LDLR to enhance steroidogenesis regarding the effect of lovastatin in the CCs. The collection of human cumulus cells was approved by the Institutional Research and Ethical Committees of CHA University (approval number: 1044308–201611-BR–027–04) from January to December 2019. The CCs were collected from 12 patients with normal ovarian response after oocyte denudation for ICSI. Participants/materials, setting, methods We studied whether lovastatin has up-regulated LDLR expression in human CCs. Cumulus cells were collected from patients with young (∼ 36) and old aged patients (37 ∼). After culturing human CCs, they were treated lovastatin for one day. The concentration of E2 in culture medium was measured using Chemiluminescence immunoassay. The mRNA isolated from CCs was analyzed gene expression level through real time-PCR. Main results and the role of chance The concentration of E2 was significantly increased in the culture medium treated with lovastatin. The CCs treated with lovastatin increased the expression of LDLR and StAR which are components of the steroidogenesis pathway. Limitations, reasons for caution We have found that the role of lovastatin promotes the E2 production by increasing the ldlr gene of CCs. Therefore, further investigations aimed at lovastatin effect on human oocytes embryo whether enhanced quality of oocytes or not. Wider implications of the findings: Previous data show that high activation of LDLR and StAR was associated with embryo quality and clinical pregnancy in infertile women. Our data suggest that lovastatin is stimulated LDLR expression to enhanced pregnancy ratios of IVF patients. Trial registration number none

Amplification of the Hazelnut-Induced Epigenetic Modulation of LDLR Gene Expression in THLE-2 Human Primary Hepatocytes Compared to HepG2 Hepatocarcinoma Cells

Dietary supplementation with tree nuts, including hazelnuts, has been associated with reduced cardiovascular disease risk factors, due to improved blood lipid profile. In the attempt to identify the molecular mechanism(s) underlying such beneficial effect, we here characterized the response of the human primary hepatocytes (THLE-2 cells) to the administration of an ethanolic extract of hazelnut (Corylus avellana L., cultivar Tonda Gentile Romana) in terms of regulation of the Low-Density Lipoprotein Receptor (LDLR), a major blood cholesterol carrier that positively correlates with improved blood lipids level. We demonstrated that hazelnut (0.004-0.4 mg/ml) does not alter viability and growth of primary liver cells, but significantly stimulates (P<0.05) the LDLR mRNA and membrane protein expression. We also proved that LDLR increase is driven by an epigenetic-based mechanism, as hazelnut treatments trigger a strong DNA hypo-methylation of two CpG-rich regions in the LDLR gene promoter, mapping at -739/-548 and -221/+174 position. The hazelnutmediated hypo-methylation is much stronger and extensive in THLE-2 than in HepG2 human hepatocarcinoma cells, supporting the significance of the liver context for performing studies on dietary supplementation. As overall, our findings demonstrate that hazelnut triggers an epigenetic-dependent regulation of LDLR expression in human primary liver cells in vitro, thus identifying in the LDLR stimulation a molecular mechanism contributing to the health promoting functions of hazelnuts.

Ameliorative Effect of Trigonella Foenum Graecum L. on Lipid Profile, Liver Histology and LDL-Receptor Gene Expression in High Cholesterol-Fed Hamsters.

Trigonella foenum graecum L. (Fenugreek, FG) is used in many countries as a medicinal plant. Evidence has suggested the hypolipidemic effect of Fenugreek; however, its actual mechanism has not been determined yet. The purpose of our research was to investigate the effect of Fenugreek on lipid profile, liver histology and LDL receptor gene expression in male hamsters fed with high cholesterol diet. These animals were given normal diet (ND), high cholesterol diet (HCD: 2% cholesterol and 0.5% cholic acid added to ND), HCD supplemented with 2g and 8g fenugreek per 100g ND (HCD+FG2 and HCD+FG8) respectively for four weeks. At the end of treatment, serum lipids, lipoproteins and liver enzymes were measured. Finally, LDL receptor (LDLR) gene expression was determined in the liver of the studied animals using Real Time-PCR method and liver histological changes were evaluated by H&E staining method. A significant reduction was observed in serum triglyceride (p<0.01), total cholesterol, low and very low density cholesterol, aspartate and alanine transaminases in HCD+FG8 group (p<0.05) compared with HCD group, while serum level of HDL-c (p<0.01) increased. In addition, LDLR gene expression in HCD+FG8 group increased 7.8 folds. The results confirm the protection effect of liver tissue in HCD+FG8 group against pathological changes. There was no significant change in LDLR gene expression in HCD+FG2 group. In conclusion, fenugreek ameliorated dyslipidemia by up-regulation of LDLR gene expression and can be used as a protective agent against hypercholesterolemia.

R-α-Lipoic Acid and 4-Phenylbutyric Acid Have Distinct Hypolipidemic Mechanisms in Hepatic Cells.

The constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) leads to the overproduction of apoB-containing triacylglycerol-rich lipoproteins in HepG2 cells. R-α-lipoic acid (LA) and 4-phenylbutyric acid (PBA) have hypolipidemic function but their mechanisms of action are not well understood. Here, we reported that LA and PBA regulate hepatocellular lipid metabolism via distinct mechanisms. The use of SQ22536, an inhibitor of adenylyl cyclase, revealed cAMP’s involvement in the upregulation of CPT1A expression by LA but not by PBA. LA decreased the secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the culture media of hepatic cells and increased the abundance of LDL receptor (LDLR) in cellular extracts in part through transcriptional upregulation. Although PBA induced LDLR gene expression, it did not translate into more LDLR proteins. PBA regulated cellular lipid homeostasis through the induction of CPT1A and INSIG2 expression via an epigenetic mechanism involving the acetylation of histone H3, histone H4, and CBP-p300 at the CPT1A and INSIG2 promoters.

Effects of curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial

The aim of this study was to evaluate the effect of curcumin on body weight, glycemic control and serum lipids in women suffering from polycystic ovary syndrome (PCOS). The current randomized, double-blinded, placebo-controlled clinical trial was performed on 60 subjects with PCOS, aged 18-40 years old. Subjects were randomly allocated to take 500mg/day curcumin (n=30) or placebo (n= 30) for 12 weeks. Glycemic control and serum lipids were measured at baseline and after the 12-week intervention. Using RT-PCR method, gene expression related to insulin and lipid metabolism was evaluated. Curcumin significantly decreased weight (-0.8±0.9 vs.-0.2±0.8kg, P=0.03) and BMI (-0.3±0.4 vs.-0.1±0.3kg/m2, P=0.03). Curcumin, compared with the placebo, significantly reduced fasting glucose (β-2.63mg/dL; 95% CI,-4.21,-1.05; P=0.002), serum insulin (β-1.16 μIU/mL; 95% CI,-2.12,-0.19; P=0.02), insulin resistance (β-0.26; 95% CI,-0.48,-0.03; P=0.02), and significantly increased insulin sensitivity (β 0.006; 95% CI, 0.001, 0.01; P=0.02). In addition, taking curcumin was associated with a significant reduction in total cholesterol (β-15.86mg/dL; 95% CI,-24.48,-7.24; P=0.001), LDL-cholesterol (β-16.09mg/dL; 95% CI,-25.11,-7.06; P=0.001) and total-/HDL-cholesterol ratio (β-0.62; 95% CI,-0.93,-0.30; P<0.001), and a significant increase in HDL-cholesterol levels (β 2.14mg/dL; 95% CI, 0.36, 3.92; P=0.01) compared with the placebo. Additionally, curcumin administration up-regulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P=0.03) and low-density lipoprotein receptor (LDLR) (P<0.001) compared with the placebo. Overall, curcumin administration for 12 weeks to women with PCOS had beneficial effects on body weight, glycemic control, serum lipids except triglycerides and VLDL-cholesterol levels, and gene expression of PPAR-γ and LDLR. Registered under Clinical Trials.gov Identifier no. http://www.irct.ir: IRCT20170513033941N50.

The Effects of Selenium Supplementation on Gene Expression Related to Insulin and Lipid Metabolism, and Pregnancy Outcomes in Patients with Gestational Diabetes Mellitus: a Randomized, Double-Blind, Placebo-Controlled Trial.

This study was performed to evaluate the effects of selenium supplementation on gene expression related to insulin and lipid metabolism, and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). The current randomized, double-blind, placebo-controlled clinical trial was conducted in 36 patients with GDM. Participants were randomly divided into two groups to intake either 200μg/day selenium supplements as selenium yeast or placebo (n = 18 each group) for 6weeks. Selenium supplementation upregulated peroxisome proliferator-activated receptor gamma (P = 0.03) and glucose transporter 1 (GLUT-1) (P = 0.01) in lymphocytes of subjects with GDM compared with the placebo. Selenium supplementation did not affect gene expression of low-density lipoprotein receptor (LDLR) and lipoprotein(a) [Lp(a)]. Supplementation with selenium had a significant decrease in incidence of newborns' hyperbilirubinemia (5.6% vs. 33.3%, P = 0.03) and newborns' hospitalization (5.6% vs. 33.3%, P = 0.03) compared with the placebo. Overall, we found that selenium supplementation for 6weeks among patients with GDM significantly increased PPAR-γ and GLUT-1 expression, but did not affect gene expression of LDLR and LP(a). It also reduced incidence of newborns' hyperbilirubinemia and newborns' hospitalization. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N35.

A Structured Pine Nut Oil Has Hypocholesterolemic Activity by Increasing LDLR Gene Expression in the Livers of Obese Mice

A structured pine nut oil (SPNO) is previously developed with pinolenic acid (PLA) evenly distributed at all sn positions on the glycerol backbone, whereas natural pine nut oil (NPNO) has PLA positioned mostly at the sn‐3 position. This SPNO exhibited greater lymphatic PLA absorption than NPNO, although SPNO and NPNO contained equal amounts (≈13 wt%) of PLA. In this study, SPNO containing ≈13 wt% PLA (SPNO13) and ≈44 wt% PLA (SPNO44) is produced via Novozym 435‐catalyzed esterification of glycerol with the free fatty acids containing ≈13 wt% and ≈44 wt% PLA from NPNO (from Pinus koraiensis Siebold &amp; Zucc.). Five‐week‐old C57/BL6J mice are fed either a low‐ or high‐fat diet (HFD) containing NPNO, SPNO13, or SPNO44 for 15 weeks. Supplementation with SPNO44, but not NPNO or SPNO13, significantly attenuates HFD‐induced increases in final body weight, weight gain, and retroperitoneal and liver masses in diet‐induced obese mice, without affecting food intake. SPNO44 also significantly reduces serum total and LDL cholesterol levels, as well as serum triacylglycerol levels and hepatic lipid accumulation. The hypocholesterolemic activity of SPNO44 is attributed to the greater hepatic accumulation of PLA from it causing increased SREBP2 levels and upregulation of LDL receptor gene expression in the livers of obese mice.Practical Applications: PLA has received much attention due to its anti‐obesity and anti‐dyslipidemia effects. NPNO is the sole source of PLA, but it can be converted into SPNO. The authors hypothesized that SPNO should improve PLA's health benefits due to the enhanced lymphatic absorption of PLA from SPNO. When compared to NPNO, SPNO44 may provide several advantages, such as enhanced anti‐obesity and anti‐dyslipidemia effects for food and nutraceutical applications. In future studies, the lymphatic absorption of SPNO44 and NPNO or SPNO13 should be compared.SPNO44, a structured pine nut oil containing ≈44 wt% pinolenic acid (PLA) and an even distribution of PLA on the glycerol backbone, has hypocholesterolemic activity by increasing sterol regulatory element‐binding protein 2 (SREBP2) levels and upregulating LDLR gene expression in the livers of obese mice.

Effects of melatonin administration on mental health parameters, metabolic and genetic profiles in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial

ObjectiveThe aim of this study was to evaluate the effect of melatonin supplementation on mental health parameters, metabolic and genetic parameters in women suffering from polycystic ovary syndrome (PCOS). MethodsThis randomized, double-blinded, placebo-controlled clinical trial was performed on 58 subjects, aged 18–40 years old. Subjects were randomly allocated to take either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 29) or placebo (n = 29) once a day 1 h before bedtime for 12 weeks. Glycemic control and lipid profiles were measured at baseline and after the 12-week intervention. Using RT-PCR method, gene expression related to insulin and lipid metabolism was conducted on peripheral blood mononuclear cells (PBMCs) of PCOS women. ResultsMelatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (β −2.15; 95% CI, −3.62, −0.68; P = 0.005), Beck Depression Inventory index (β −3.62; 95% CI, −5.53, −1.78; P<0.001) and Beck Anxiety Inventory index (β −1.95; 95% CI, −3.41, −0.48; P = 0.01) compared with the placebo. In addition, melatonin administration, compared with the placebo, significantly reduced serum insulin (β −1.20 µIU/mL; 95% CI, −2.14, −0.26; P = 0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (β −0.28; 95% CI, −0.50, −0.05; P = 0.01), serum total- (β −7.96 mg/dL; 95% CI, −13.75, −2.17; P = 0.008) and LDL-cholesterol levels (β −5.88 mg/dL; 95% CI, −11.42, −0.33; P = 0.03), and significantly increased the quantitative insulin sensitivity check index (QUICKI) (β 0.008; 95% CI, 0.002, 0.014; P = 0.007). Moreover, melatonin supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.004) and low-density lipoprotein receptor (LDLR) (P = 0.01) compared with the placebo. ConclusionsOverall, melatonin administration for 12 weeks had beneficial effects on mental health parameters, insulin levels, HOMA-IR, QUICKI, total- and LDL-cholesterol levels, and gene expression of PPAR-γ and LDLR among women with PCOS.

The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial

ObjectiveThis study was conducted to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in subjects with Parkinson's disease (PD). Patients and methodsThis randomized, double-blind, placebo-controlled clinical trial was performed in 40 subjects with PD. Participants were randomly allocated into two groups to take either 1000 mg/day of omega-3 fatty acids from flaxseed oil plus 400 IU/day of vitamin E supplements or placebo (n = 20 each group) for 12 weeks. Gene expression related to inflammation, insulin and lipid were quantified in peripheral blood mononuclear cells (PBMC) of PD patients with RT-PCR method. ResultsAfter the 12-week intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation downregulated gene expression of tumor necrosis factor alpha (TNF-α) (P = 0.002) in PBMC of subjects with PD. In addition, omega-3 fatty acids and vitamin E co-supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03), and downregulated oxidized low-density lipoprotein receptor (LDLR) (P = 0.002) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of omega-3 fatty acids and vitamin E co-supplementation on gene expression of interleukin-1 (IL-1) and IL-8 in PBMC of patients with PD. ConclusionsOverall, omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in PD patients significantly improved gene expression of TNF-α, PPAR-γ and LDLR, but did not affect IL-1 and IL-8.

The Effects of Chromium Supplementation on Gene Expression of Insulin, Lipid, and Inflammatory Markers in Infertile Women With Polycystic Ovary Syndrome Candidate for in vitro Fertilization: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Purpose: This study was performed to determine the effects of chromium supplementation on the gene expression of insulin, lipid, and inflammatory markers in infertile women with polycystic ovary syndrome (PCOS) who were candidate for in vitro fertilization (IVF).Methods: Forty women, aged 18–40 years, who had been selected for IVF were recruited in this randomized double-blinded, placebo-controlled trial. They (n = 20/group) were randomly assigned into intervention groups to take either 200 μg/day of chromium or placebo for 8 weeks. Inflammatory markers were measured at baseline and end of the trial. Genes related to insulin, lipid, and inflammation were expressed in peripheral blood mononuclear cells (PBMCs), using RT-PCR method.Results: Chromium supplementation led to a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (−1.4 ± 1.5 vs. + 0.2 ± 2.2 mg/L, p = 0.01) compared with the placebo. RT-PCR findings indicated that chromium supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (p = 0.01), glucose transporter 1 (GLUT-1) (p = 0.001) and low-density lipoprotein receptor (LDLR) (p = 0.01), as well as downregulated gene expression of interleukin-1 (IL-1) (p = 0.004) in PBMCs of patients with PCOS compared with the placebo. Chromium supplementation had no significant effect on gene expression of IL-8, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF).Conclusion: Overall, our findings demonstrated that infertile women with PCOS, who were candidate for IVF benefited from chromium supplementation for 8 weeks in terms of lowering hs-CRP and improving gene expression of PPAR-γ, GLUT-1, LDLR, and IL-1, though chromium had no effect on the gene expression of IL-8, TNF-α, TGF-β, and VEGF.Clinical Trial Registration Number: http://www.irct.ir:IRCT20170513033941N32.

Regulatory effect of Phikud Navakot extract on HMG-CoA reductase and LDL-R: potential and alternate agents for lowering blood cholesterol

BackgroundFor decades, various cardiovascular symptoms have been relieved by the use of Ya-Hom Navakot, which is a formulation comprising 54 herbal medicines. The Thailand Ministry of Public Health listed Ya-Hom Navakot’s nine active principle and nomenclative herbal ingredients and termed them ‘Phikud Navakot’ (PN). Several reports have confirmed that PN has cardiovascular benefits similar to Ya-Hom Navakot. However, whether PN facilitates lipid-lowering activity remains unclear.MethodsThe present study investigated an in vitro model for examining the gene expression levels of 3-hydroxyl-3-methylglutaryl-CoA reductase (HMGCR) and low-density lipoprotein receptor (LDL-R) in HepG2 cells using qRT-PCR. The ethanol and water extractions of Ya-Hom Navakot, PN and Ya-Hom Navakot without PN were compared.ResultsOne mg/ml of both NYEF and NYWF were found to significantly lower cholesterol by either the up-regulation of LDL-R or down-regulation of HMGCR compared with negative controls and 1 mg/ml simvastatin (p < 0.05). PNEF also up-regulated LDL-R gene expression, even more than NYEF (p < 0.05). In addition, the ethanol and water extracts of PN significantly down-regulated HMGCR gene expression compared with those of Ya-Hom Navakot without PN (p < 0.05).ConclusionThe use of Ya-Hom Navakot or PN may provide an alternative treatment to lower cholesterol through HMGCR gene inhibition and LDL-R gene enhancement.

Dill-normalized liver lipid accumulation, oxidative stress, and low-density lipoprotein receptor levels in high cholesterol fed hamsters.

BACKGROUNDHigh lipid accumulation in hepatocyte and blood vessels can lead to non-alcoholic fatty liver disease (NAFLD) and heart diseases, respectively. These disorders are the main reasons of mortality in various countries. In this experiment, we evaluated the effect of leaf extracts of Anethum graveolens (AG), also known as Dill, and AG tablet on expression of low-density lipoprotein receptor (LDLR) and liver lipid in hypercholesterolemic hamsters.METHODSIn this experimental study, 36 male golden hamsters were divided into 6 groups: 1) standard diet + 0.5% cholic acid + 2% cholesterol [high cholesterol diet (HCD)], 2) HCD + 100 mg/kg hydroalcoholic extract of Dill, 3) HCD + 200 mg/kg hydroalcoholic extract of Dill, 4) HCD + 100 mg/kg Dill tablet, 5) HCD + 200 mg/kg Dill tablet, 6) chow. At the end of study (30th day), hamsters were anesthetized and blood sample and liver tissue were collected. Biochemical factors and antioxidant parameters were determined. LDLR messenger ribonucleic acid (mRNA) level was measured using real time polymerase chain reaction (RT-PCR). Histopathological change of liver was determined using light microscope.RESULTSCompared to HCD group, blood lipids (P < 0.0010) and liver enzymes (P < 0.0010) markedly reduced in AG-treated groups. The expression of LDLR did not change significantly in animals which received low dose of hydroalcoholic extract or AG tablet, but it increased in animals receiving high dose of extract or tablet (P < 0.0100). Liver antioxidant significantly increased by AG (P < 0.0010). Liver histopathological changes were normalized by AG.CONCLUSIONAG can significantly increase LDLR gene expression in HCD animals. This study showed that both AG extract and AG tablet had potential antioxidant and hypolipidemic effects in hamsters.

Intake of sfa compared to pufa induce lower postprandial ldl receptor gene expression in pbmc in subjects with and without FH

Intake of sfa compared to pufa induce lower postprandial ldl receptor gene expression in pbmc in subjects with and without FH

Ground Beef High in Total Fat and Saturated Fatty Acids Decreases X Receptor Signaling Targets in Peripheral Blood Mononuclear Cells of Men and Women.

We hypothesized that consumption of saturated fatty acids in the form of high-fat ground beef for 5 weeks would depress liver X receptor signaling targets in peripheral blood mononuclear cells (PBMC) and that changes in gene expression would be associated with the corresponding changes in lipoprotein cholesterol (C) concentrations. Older men (n = 5, age 68.0 ± 4.6 years) and postmenopausal women (n = 7, age 60.9 ± 3.1 years) were assigned randomly to consume ground-beef containing 18% total fat (18F) or 25% total fat (25F), five patties per week for 5 weeks with an intervening 4-week washout period. The 25F and 18F ground-beef increased (p < 0.05) the intake of saturated fat, monounsaturated fat, palmitic acid, and stearic acid, but the 25F ground-beef increased only the intake of oleic acid (p < 0.05). The ground-beefs 18F and 25F increased the plasma concentration of palmitic acid (p < 0.05) and decreased the plasma concentrations of arachidonic, eicosapentaenoic, and docosahexaenic acids (p < 0.05). The interventions of 18F and 25F ground-beef decreased very low-density lipoprotein C concentrations and increased particle diameters and low-density lipoprotein (LDL)-I-C and LDL-II-C concentrations (p < 0.05). The ground-beef 25F decreased PBMC mRNA levels for the adenosine triphosphate (ATP) binding cassette A, ATP binding cassette G1, sterol regulatory element binding protein-1, and LDL receptor (LDLR) (p < 0.05). The ground-beef 18F increased mRNA levels for stearoyl-CoA desaturase-1 (p < 0.05). We conclude that the increased LDL particle size and LDL-I-C and LDL-II-C concentrations following the 25F ground-beef intervention may have been caused by decreased hepatic LDLR gene expression.

The effects of fish oil on gene expression in patients with polycystic ovary syndrome.

This study was conducted to determine the effects of fish oil administration on gene expression related to insulin, lipid and inflammation in women with polycystic ovary syndrome (PCOS). This randomized, double-blind, placebo-controlled trial was conducted among 40 subjects with PCOS, aged 18-40 years. Subjects were randomly allocated into two groups to take either 1000 mg omega-3 fatty acids from fish oil (n = 20) or placebo (n = 20) twice a day for 12 weeks. Gene expression related to insulin, lipid and inflammation was quantified in peripheral blood mononuclear cells (PBMC) of PCOS women with RT-PCR method. Our study demonstrated that after the 12-week intervention, compared with the placebo, fish oil supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < .001) in PBMC of subjects with PCOS. In addition, compared to the placebo, taking fish oil supplements downregulated gene expression of interleukin-1 (IL-1) (P = .02) and interleukin-8 (IL-8) (P = .01) in PBMC of subjects with PCOS. We did not observe any significant effect of fish oil supplementation on gene expression of lipoprotein(a) [LP(a)], low-density lipoprotein receptor (LDLR), glucose transporter 1 (GLUT-1), tumour necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) in PBMC of subjects with PCOS. Overall, fish oil supplementation for 12 weeks to subjects with PCOS significantly improved gene expression of PPAR-γ, IL-1 and IL-8, but did not influence gene expression of LP(a), LDLR, GLUT-1, TNF-α and TGF-β.