scholarly journals miR-34a-5p Increases Hepatic Triglycerides and Total Cholesterol Levels by Regulating ACSL1 Protein Expression in Laying Hens

2019 ◽  
Vol 20 (18) ◽  
pp. 4420 ◽  
Author(s):  
Wei-Hua Tian ◽  
Zhang Wang ◽  
Ya-Xin Yue ◽  
Hong Li ◽  
Zhuan-Jian Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Total Cholesterol ◽  
Lipid Content ◽  
Target Gene ◽  
Laying Hens ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Regulatory Molecule ◽  
Cholesterol Levels ◽  
Chain Acyl

Accumulating evidence has shown that miR-34a serves as a posttranscriptional regulatory molecule of lipid metabolism in mammals. However, little studies about miR-34a on lipid metabolism in poultry have been reported until now. To gain insight into the biological functions and action mechanisms of miR-34a on hepatic lipid metabolism in poultry, we firstly investigated the expression pattern of miR-34a-5p, a member of miR-34a family, in liver of chicken, and determined its function in hepatocyte lipid metabolism by miR-34a-5p overexpression and inhibition, respectively. We then validated the interaction between miR-34a-5p and its target using dual-luciferase reporter assay, and explored the action mechanism of miR-34a-5p on its target by qPCR and Western blotting. Additionally, we looked into the function of the target gene on hepatocyte lipid metabolism by gain- and loss-of-function experiments. Our results indicated that miR-34a-5p showed a significantly higher expression level in livers in peak-laying hens than that in pre-laying hens. miR-34a-5p could increase the intracellular levels of triglycerides and total cholesterol in hepatocyte. Furthermore, miR-34a-5p functioned by inhibiting the translation of its target gene, long-chain acyl-CoA synthetase 1 (ACSL1), which negatively regulates hepatocyte lipid content. In conclusion, miR-34a-5p could increase intracellular lipid content by reducing the protein level, without influencing mRNA stability of the ACSL1 gene in chickens.

Hypothyroidism affects lipid and glycogen content and peroxisome proliferator-activated receptor δ expression in the ovary of the rabbit

2018 ◽  
Vol 30 (10) ◽  
pp. 1380 ◽  
Author(s):  
Julia Rodríguez-Castelán ◽  
Maribel Méndez-Tepepa ◽  
Jorge Rodríguez-Antolín ◽  
Francisco Castelán ◽  
Estela Cuevas-Romero
Keyword(s):  
Lipid Metabolism ◽  
Total Cholesterol ◽  
Lipid Content ◽  
Glycogen Content ◽  
Ovarian Cysts ◽  
Oxidized Lipids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Perilipin A ◽  
Follicle Maturation

Dyslipidaemia and hyperglycaemia are associated with ovarian failure and both have been related to hypothyroidism. Hypothyroidism promotes anovulation and ovarian cysts in women and reduces the size of follicles and the expression of aromatase in the ovary of rabbits. Considering that ovarian steroidogenesis and ovulation depend on lipid metabolism and signalling, the aim of the present study was to analyse the effect of hypothyroidism on the lipid content and expression of peroxisome proliferator-activated receptor (PPAR) δ in the ovary. Ovaries from female rabbits belonging to the control (n = 7) and hypothyroid (n = 7) groups were processed to measure total cholesterol (TC), triacylglycerol (TAG) and glycogen content, as well as to determine the presence of granules containing oxidized lipids (oxysterols and lipofuscin) and the relative expression of perilipin A (PLIN-A) and PPARδ. Hypothyroidism increased TC and glycogen content, but reduced TAG content in the ovary. This was accompanied by a reduction in the expression of PLIN-A in total and cytosolic extracts, changes in the presence of granules containing oxidative lipids and low PPARδ expression. The results of the present study suggest that hypothyroidism modifies the content and signalling of lipids in the ovary, possibly affecting follicle maturation. These results could improve our understanding of the association between hypothyroidism and infertility in females.

013 Lipid metabolism and body composition in frontotemporal dementia-amyotrophic lateral sclerosis spectrum: effect on survival and disease progression

2018 ◽  
Vol 89 (6) ◽  
pp. A6.3-A7
Author(s):  
Rebekah M Ahmed ◽  
Elizabeth Highton-Williamson ◽  
Jashelle Caga ◽  
Nicollette Thornton ◽  
Eleanor Ramsey ◽  
...  
Keyword(s):  
Body Composition ◽  
Lipid Metabolism ◽  
Total Cholesterol ◽  
Eating Behaviour ◽  
Density Lipoprotein ◽  
Cognitive Change ◽  
Fat Intake ◽  
Cholesterol Levels ◽  
Als Patients ◽  
Lateral Sclerosis

IntroductionPatients with Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) exhibit changes in eating behaviour that could potentially affect lipid levels and body composition. This study aimed to document changes in lipid metabolism and body composition across the ALS-FTD spectrum to identify potential relationships to eating behaviour (including fat intake), cognitive change, body mass index (BMI) and effect on survival.MethodsOne hundred and twenty eight participants were recruited: 37 ALS patients, 15 ALS patients with cognitive and behavioural change (ALS-Plus), and 13 ALS-FTD, 31 behavioural variant FTD, and 32 healthy controls. Fasting total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and triglyceride levels were measured and correlated to eating behaviour (caloric, fat intake), cognitive change, and BMI; effect on survival was examined using cox regression analyses. In a cohort of 60 patients, changes in body composition and fat deposition was examined using Dual energy X-ray absorptiometry scans (DEXA), a technique used in obesity research.ResultsThere was a spectrum of lipid changes from ALS to FTD with increased triglyceride (p<0.001), total cholesterol/HDL ratio (p<0.001), and lower HDL levels (p=0.001) in all patient groups compared to controls. Whilst there was no increase in total cholesterol levels, a higher cholesterol level was found to correlate with 3.25 times improved survival (p=0.031). Triglyceride and HDL cholesterol correlated to fat intake, BMI, and measures of cognition andConclusionA spectrum of changes in lipid metabolism and body composition has been identified in ALS-FTD, with total cholesterol levels found to potentially impact on survival. These changes were mediated by changes in fat intake, and BMI, and may also be mediated by the neurodegenerative process, offering the potential to modify these factors to slow disease progression and improve survival.

scholarly journals Bta-miR-124a Affects Lipid Metabolism by Regulating PECR Gene

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Binglei Shen ◽  
Zhuonina Yang ◽  
Shuo Han ◽  
Ziwen Zou ◽  
Juan Liu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Dairy Cows ◽  
Signaling Pathway ◽  
Target Gene ◽  
Target Genes ◽  
Mammary Epithelial ◽  
Luciferase Reporter ◽  
Milk Lipid ◽  
Candidate Target

According to our previous studies, bta-miR-124a was differentially expressed in breast tissue between high-fat and low-fat dairy cows. However, the function of bta-miR-124a in lipid metabolism of dairy cows and the identification of its target genes have not been reported. Therefore, this study will identify the target gene of bta-miR-124a and explore its role in the regulation of milk lipid metabolism. First, preliminary bioinformatics prediction of bta-miR-124a candidate target genes was performed, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze relative expression changes of bta-miR-124a and its candidate target genes and the expression level of the downstream gene of the target gene in the lipid metabolism signaling pathway in dairy mammary epithelial cell lines (Mac-T), using the dual luciferase reporter system for the identification of the targeting relationship between bta-miR-124a and the candidate target gene. Then, the effect of transfection of bta-miR-124a mimics and inhibitors on triglyceride (TG) and free fatty acid (FFA) levels was analyzed. The results indicate that bta-miR-124a directly interacts with the 3′-untranslated region of peroxisomal trans-2-enoyl-CoA reductase (PECR) to downregulate its expression in Mac-T cells. Further, bta-mir-124a regulates the expression of PECR and the downstream gene extension of very long chain fatty acid protein 2 (ELOVL2) through an unsaturated fatty acid biosynthesis signaling pathway. In conclusion, bta-miR-124a is involved in lipid metabolism by directly downregulating the PECR gene and affecting the expression of the downstream gene ELOVL2 and regulates the content of some key secretory elements such as TG and FFA. The function of bta-miR-124a has a certain effect on the synthesis and secretion of milk fat in the mammary epithelial cells of dairy cows.

scholarly journals miR-362-3p acts as a tumor suppressor by targeting SERBP1 in ovarian cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shujun Cao ◽  
Na Li ◽  
Xihong Liao
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Gynecological Cancer ◽  
Luciferase Reporter ◽  
Loss Of Function

Abstract Background Ovarian cancer is the leading lethal gynecological cancer and is generally diagnosed during late-stage presentation. In addition, patients with ovarian cancer still face a low 5-year survival rate. Thus, innovative molecular targeting agents are required to overcome this disease. The present study aimed to explore the function of miR-362-3p and the underlying molecular mechanisms influencing ovarian cancer progression. Methods The expression levels of miR-362-3p were determined using qRT-PCR. Gain-of-function and loss-of-function methods were used to detect the effects of miR-362-3p on cell proliferation, cell migration, and tumor metastasis in ovarian cancer. A luciferase reporter assay was performed to confirm the potential target of miR-362-3p, and a rescue experiment was employed to verify the effect of miR-362-3p on ovarian cancer by regulating its target gene. Results miR-362-3p was significantly downregulated in ovarian cancer tissues and cell lines. In vitro, our data showed that miR-362-3p suppressed cell proliferation and migration. In vivo, miR-362-3p inhibited ovarian cancer growth and metastasis. Mechanistically, SERBP1 was identified as a direct target and functional effector of miR-362-3p in ovarian cancer. Moreover, SERBP1 overexpression rescued the biological function of miR-362-3p. Conclusions Our data reveal that miR-362-3p has an inhibitory effect on ovarian cancer. miR-362-3p inhibits the development and progression of ovarian cancer by directly binding its target gene SERBP1.

scholarly journals miR-17~92 Promotes Progression of ABC-DLBCL Lymphoma via Regulation of Canonical NF-kB Signaling

2021 ◽  
Author(s):  
Xianhuo Wang ◽  
Huaqing Wang ◽  
Xiaoyan Zhang ◽  
Chengfeng Bi ◽  
Timothy W. McKeithan ◽  
...  
Keyword(s):  
B Cell ◽  
Therapeutic Strategy ◽  
Target Gene ◽  
Target Genes ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Over Expression ◽  
Dual Luciferase Reporter Assay

Abstract Background: Activated B-cell like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoma characterized by constitutive NF-κB activation. Nevertheless, the role and mechanisms of miR-17~92 in contributing to the NF-κB activation in ABC-DLBCL are still elusive. Methods: The expression of miR-17~92 primary transcript (MIR17HG) and NF-κB target genes was determined using RNA-sequencing. The expression of miR-17~92 was performed using microarray analysis. Plasmids carrying conditional over-expression and loss-of-function of miR-17~92 were respectively constructed and dual-luciferase reporter assay was used to validate the target gene of miR-17~92. Immunoprecipitation and polyubiquitination were further used to the study of potential mechanisms.Results: Expression of MIR17HG was positively correlated with NF-κB activity, miR-17~92 activated the NF-κB signaling in ABC-DLBCL, and its over-expression promoted ABC-DLBCL cell growth, accelerated cell G1 to S phase transition and enhanced cell resistance to NF-κB inhibitor. Importantly, miR-17~92 promoted NF-κB activation through directly targeting multiple ubiquitin-editing regulators to lead to increase the K63-linked polyubiquitination and decrease the K48-linked polyubiquitination of RIP1 complex in ABC-DLBCL. We further found that miR-17~92 selectively activated IκB-α and NF-κB p65 but not NF-κB p52/p100, and high miR-17~92 expression was also associated with poorer outcome in ABC-DLBCL patients. Conclusions: Taken together, miR-17~92 selectively activate the canonical NF-κB signaling via targeting ubiquitin-editing regulators to lead to constitutively NF-κB activation and poorer outcome, which is an innovative function of miR-17~92 and previously unappreciated regulatory mechanism of NF-κB activation in ABC-DLBCL. Targeting miR-17~92 may thus provide a novel bio-therapeutic strategy for ABC-DLBCL patients.

scholarly journals ANGPLT3: A novel modulator of lipid metabolism

2017 ◽  
Vol 2017 (1) ◽  
Author(s):  
Mohamed Hassan
Keyword(s):  
Lipid Metabolism ◽  
Endothelial Lipase ◽  
Loss Of Function ◽  
New Class ◽  
Irreversible Inhibition ◽  
Cholesterol Levels ◽  
Important Regulator ◽  
Activity Loss ◽  
Regulate Lipid Metabolism ◽  
Novel Therapeutic

Angiopoietin-like proteins (ANGPTLs) have emerged as an important regulator of lipid and glucose metabolism as well as insulin sensitivity. ANGPTL3 plays a key role in regulating circulating triglycerides (TG) and cholesterol levels through reversible inhibition of lipoprotein lipase (LPL) and endothelial lipase enzymes activity. Loss of function mutation of ANGPTL3 gene has been identified in many subjects with familial combined hypolipidemia. ANGPTL4 produces irreversible inhibition of LPL activity, while ANGPTL8 enhances the activity of ANGPTL3, which highlight the interplay between the different ANGPTLs in a coordinated manner to regulate lipid metabolism during different nutritional states. This new class of lipid modulators may serve as potential novel therapeutic target for reducing plasma lipoprotein and treatment of metabolic syndrome. 

Effect of triglyceride and total cholesterol levels on the pharmacokinetics of clozapine in clozapine medicated patients

2016 ◽  
Vol 49 (03) ◽  
Author(s):  
G Schoretsanitis ◽  
S Lammertz ◽  
C Hiemke ◽  
G Janssen ◽  
G Gründer ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Cholesterol Levels

Pengaruh Pemberian Terapi Oksigen Hiperbarik Terhadap Kadar Kolesterol Total Pada Tikus Putih (Rattus novergicus) Jantan Galur Wistar Yang Di Induksi Diet Tinggi Lemak

2018 ◽  
Vol 16 (1) ◽  
pp. 1 ◽  
Author(s):  
AZRUL HILDAN SAFRIZAL
Keyword(s):  
Cardiovascular Disease ◽  
Total Cholesterol ◽  
Cholesterol Level ◽  
Hyperbaric Oxygen ◽  
Hyperbaric Oxygen Therapy ◽  
High Fat Diet ◽  
Oxygen Therapy ◽  
Total Cholesterol Level ◽  
High Fat ◽  
Cholesterol Levels

<p>The pattern and lifestyle of today's society with the presence of an interner facility makes people spend more time sitting out than on exercise and increased consumption of high-fat foods may increase the risk of cardiovascular disease. An effective therapy is needed in preventing the occurrence of cardiovascular disease. Hyperbaric oxygen now starts to develop for the treatment of several diseases, which in turn can increase the gene forming antioxidant enzymes and ROS. To determine effect of hyperbaric oxygen therapy on total cholesterol levels of wistar white rats (Rattusnovergicus) induced bye high fat. The study was carried out in an expeative post test only group control of three groups. One group is given standard feed. All groups induced high-fat diet and standard feed. Of the two groups induced, one group was given hyperbaric oxygen therapy with a dose of 3 x 30 minutes for six days on day 7 at a blood test to determine total cholesterol levels<strong>. </strong>One way Anova parametric statistic test showed that p = 0.007 &lt; α proved hypothesis that hyperbaric oxygen therapy giving effect to total cholesterol level of white mice of jantangalurist rings induced by high fat diet. Total cholesterol was significantly different between K (-) and K (+) and between K (-) and P. It was found that hyperbaric oxygen therapy had an effect on total cholesterol level dose of 3x30 minutes for six days.</p>

Aktivitas Antihiperkolesterolemia Ekstrak Etanol Daun Stevia Rebaudiana Bertoni Pada Tikus Putih Jantan

2020 ◽  
Vol 2 (1) ◽  
pp. 11-20
Author(s):  
Meta Kartika Untari ◽  
Ganet Elo Pramukantoro
Keyword(s):  
Total Cholesterol ◽  
Total Cholesterol Level ◽  
Density Lipoprotein ◽  
Stevia Rebaudiana ◽  
Negative Control ◽  
Stevia Rebaudiana Bertoni ◽  
Cholesterol Levels ◽  
Water Solvent ◽  
White Rats ◽  
Group I

Hypercholesterolemia is a state of increased levels of LDL (Low Density Lipoprotein) and total cholesterol in the plasma. Stevia leaves have benefits to overcome hypercholesterolemia. The aimed of this study was to obtain ethanol extracts of Stevia rebaudiana Bertoni leaves which have activity to reduce total cholesterol levels in patients with hypercholesterolemia with effective doses. The method that will be carried out to achieve this goal was to make extracts by maceration of Stevia rebaudiana Bertoni leaf powder using a water solvent for 5 days. Testing antihypercholesterolemia activity by giving treatment to 20 male white rats. Rats were divided into 5 treatment groups. Group I was negative control, II was simvastatin control, III extract was 30 mg / 200 g BW, IV extract was 60 mg / 200 g BW, V extract was 120 mg / 200 g BW. The mice were induced by propylthiouracil 12.5 mg / day and high-fat feed for 21 days, after which the rats were given the test for 14 days. Cholesterol levels were measured on days 0, 21st and 28th. The method of determining cholesterol levels uses the Easy Touch tool. On the 35th day, a total cholesterol level was examined and data analysis was performed. The results showed that the ethanol extract of stevia leaves had antihypercholesterolemia activity, extract dose of 30 mg / 200 g BW had antihypercholesterolemia activity which was equivalent to simvastatin.

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