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. 

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.

scholarly journals High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1740
Author(s):  
Yuning Pang ◽  
Xiang Xu ◽  
Xiaojun Xiang ◽  
Yongnan Li ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Lipid Synthesis ◽  
Fat Deposition ◽  
Liver Fat ◽  
Lipid Homeostasis ◽  
High Fat ◽  
Dual Inhibitor ◽  
Regulate Lipid Metabolism

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.

Mo-P6:396 Novel DNA sequence variations in endothelial lipase gene in subjects with high HDL-cholesterol levels

2006 ◽  
Vol 7 (3) ◽  
pp. 133
Author(s):  
A. Cenarro ◽  
F. Ghisoni ◽  
P. Martín-Fuentes ◽  
D. Recalde ◽  
A.L. García-Otín ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Hdl Cholesterol ◽  
Endothelial Lipase ◽  
Lipase Gene ◽  
Cholesterol Levels ◽  
Sequence Variations

Drugs that Mimic the Effect of Gene Mutations for the Prevention or the Treatment of Atherosclerotic Disease: From PCSK9 Inhibition to ANGPTL3 Inactivation

2019 ◽  
Vol 24 (31) ◽  
pp. 3638-3646 ◽  
Author(s):  
Vasilios G. Athyros ◽  
Niki Katsiki ◽  
Aikaterini Dimakopoulou ◽  
Dimitrios Patoulias ◽  
Sofia Alataki ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Drug Treatment ◽  
Phase 1 ◽  
Micro Rna ◽  
Loss Of Function ◽  
Cvd Risk ◽  
Statin Intolerance ◽  
Hypolipidemic Drug ◽  
Cardiovascular Morbidity And Mortality ◽  
The Future

Background: Drugs mimicking natural beneficial mutations, including that for familial hypercholesterolemia (FH), might represent the future of hypolipidemic drug treatment. Objective: The aim of this review is to review the properties and the effects of these drugs, which are either already commercially available or are in the process to be approved for the treatment of dyslipidemia. Results: More than a decade ago, it was accidentally discovered that proprotein convertase subtilisin/kexin type 9 (PCSK9) loss-of-function mutations resulted in marked lifelong reduction of LDL-C and the incidence of cardiovascular disease (CVD). This provided the idea for a human anti-PCSK9 antibody. Along with dozens of phase II and III studies demonstrating unprecedented reductions in LDL-C levels, two large clinical trials established the substantial benefits of evolocumab and alirocumab on cardiovascular morbidity and mortality, on top of standard treatment. Evolocumab and alirocumab are now approved and used in clinical practice for the treatment of FH, statin intolerance, and high risk patients not achieving LDL-C targets. Anti RNA, small molecules, peptides and also protein fragments against PCSK9 are in phase 1 trials. Angiopoietin-like protein 3 (ANGPTL3) regulates lipid metabolism increasing triglycerides (TGs), remnants, and LDL-C. In a huge study, ANGPTL3 deficiency due to gene(s) loss-of-function was associated with substantial reductions in circulating TGs, LDL-C, and CVD. Evinacumab, an ANGPTL3 antibody, caused a dose-dependent reduction in fasting TG levels of up to 76% and LDL-C of up to 23% and CVD risk by 41%. There is also antisense oligonucleotide and micro-RNA- 27b (miR-27b) against ANGPTL3. Two naturally occurring mutations in apo3 gene, A23T and K58E, reduce TGs and CVD risk. A monoclonal antibody targeting apoC-III has the same effect. Conclusion: Mimicking the beneficial naturally happening mutations in lipid metabolism pathways with biological drugs is probably the future of hypolipidemic drug treatment.

scholarly journals Hepatocyte-specific Sirt6 deficiency impairs ketogenesis

2018 ◽  
Vol 294 (5) ◽  
pp. 1579-1589 ◽  
Author(s):  
Lei Chen ◽  
Qinhui Liu ◽  
Qin Tang ◽  
Jiangying Kuang ◽  
Hong Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
Critical Role ◽  
Gene Promoter ◽  
Camp Response Element Binding ◽  
Hepatic Lipid Metabolism ◽  
Camp Response Element ◽  
Hepatic Lipid ◽  
Element Binding Protein ◽  
Regulate Lipid Metabolism

Sirt6 is an NADH (NAD+)-dependent deacetylase with a critical role in hepatic lipid metabolism. Ketogenesis is controlled by a signaling network of hepatic lipid metabolism. However, how Sirt6 functions in ketogenesis remains unclear. Here, we demonstrated that Sirt6 functions as a mediator of ketogenesis in response to a fasting and ketogenic diet (KD). The KD-fed hepatocyte-specific Sirt6 deficiency (HKO) mice exhibited impaired ketogenesis, which was due to enhanced Fsp27 (fat-specific induction of protein 27), a protein known to regulate lipid metabolism. In contrast, overexpression of Sirt6 in mouse primary hepatocytes promoted ketogenesis. Mechanistically, Sirt6 repressed Fsp27β expression by interacting with Crebh (cAMP response element–binding protein H) and preventing its recruitment to the Fsp27β gene promoter. The KD-fed HKO mice also showed exacerbated hepatic steatosis and inflammation. Finally, Fsp27 silencing rescued hypoketonemia and other metabolic phenotypes in KD-fed HKO mice. Our data suggest that the Sirt6–Crebh–Fsp27 axis is pivotal for hepatic lipid metabolism and inflammation. Sirt6 may be a pharmacological target to remedy metabolic diseases.

scholarly journals Lipid profile in patients with alcohol dependence syndrome

2015 ◽  
Vol 1 (1) ◽  
pp. 29-32
Author(s):  
Mithileshwer Raut ◽  
Prashant Regmi ◽  
Saroj Prasad Ojha ◽  
Bharat Jha
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Lipid Metabolism ◽  
Alcohol Use ◽  
Alcohol Dependence ◽  
Lipid Profile ◽  
Consumption Pattern ◽  
Cholesterol Levels ◽  
Alcohol Dependence Syndrome ◽  
The Mean

BACKGROUND: Alcohol dependence syndrome (ADS) has become a global public health challenge because of its high prevalence and the concomitant increase in risk of liver disease, cardiovascular disease and premature death. Influence of alcohol use on lipid metabolism is well recognized. Investigations had been carried out in the earlier period on abnormal lipid profile as a risk factor for Coronary Heart disease (CHD). Patients of alcohol dependence usually have a consumption pattern of more heavy use. Therefore it is useful to study the lipid profile in patients of alcohol dependence, to understand the effects of increasing levels of consumption. METHODS: This cross-sectional study was conducted in TU Teaching Hospital. ADS patients were screened by the consultant psychiatrist using the Alcohol Use Disorder Identification Test (AUDIT) questionnaire. A total of 89 patients scored positive on the AUDIT as having alcohol-related problems and were included in the study. 89 ADS patients and 89 healthy controls both male and female were enrolled as participants. Blood Pressure and other anthropometric parameters were measured while fasting blood samples were analyzed for serum lipid profile. SPSS program was used to analyze data, t-test & Spearman's correlation coefficient was used to find correlation. RESULTS: Among the ADS cases 95% were current smokers. Mean age of cases and controls was 35.42±5.6 & 34.53±3.5 years respectively. The mean total cholesterol levels were found to be higher in cases (5.41±0.70) than controls (3.79±0.74) with a strong statistical significance (p<0.001). Also, Mean triglyceride (TG) levels (2.09±0.72), along with the mean HDL-cholesterol (1.66±0.40) and LDL-cholesterol levels (2.79±0.81) were also elevated in cases when compared to the control samples (p<0.001). CONCLUSION: This study has demonstrated definitive lipid profile changes in patients of alcohol dependence, with some correlation to the liver dysfunction. Alcohol causes alteration in various parameters of lipid metabolism including those which predispose to CHD. Low to moderate alcohol use over prolonged periods has been linked to have protective influence for development of coronary heart disease (CHD), through increase in high density lipoprotein cholesterol (HDL-C) levels. DOI: http://dx.doi.org/10.3126/acclm.v1i1.12312 Ann. Clin. Chem. & Lab. Med. 1(1) 2015: 29-32

scholarly journals The changes of chemerin and chemerin receptor to regulate lipid metabolism in liver and pituitary gland

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Sanggun Roh ◽  
Shun Kitayama ◽  
Astrid Ardiyanti ◽  
Yutaka Suzuki ◽  
Eri Yamauchi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Pituitary Gland ◽  
Regulate Lipid Metabolism

scholarly journals Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers

2020 ◽  
Author(s):  
Chih-Fen Hu ◽  
G. W. Gant Luxton ◽  
Feng-Chin Lee ◽  
Chih-Sin Hsu ◽  
Shih-Ming Huang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Modifiers ◽  
Loss Of Function ◽  
Dyt1 Dystonia ◽  
Whole Exome ◽  
Important Regulator ◽  
Blood Leukocyte ◽  
Aaa Protein ◽  
Neurological Movement Disorder

AbstractBackgroundDYT1 dystonia is a neurological movement disorder characterized by painful sustained muscle contractions resulting in abnormal twisting and postures. In a subset of patients, it is caused by a loss-of-function mutation (ΔE302/303; or ΔE) in the luminal ATPases associated with various cellular activities (AAA+) protein torsinA encoded by the TOR1A gene. The low penetrance of the ΔE mutation (∼30-40%) suggests the existence of unknown genetic modifiers of DYT1 dystonia.MethodsTo identify these modifiers, we performed whole exome sequencing of blood leukocyte DNA isolated from two DYT1 dystonia patients, three asymptomatic carriers of the ΔE mutation, and an unaffected adult relative.ResultsA total of 264 DYT1 dystonia-associated variants (DYT1 variants) were identified in 195 genes. Consistent with the emerging view of torsinA as an important regulator of the cytoskeleton, endoplasmic reticulum homeostasis, and lipid metabolism, we found DYT1 variants in genes that encode proteins implicated in these processes. Moreover, 40 DYT1 variants were detected in 32 genes associated with neuromuscular and neuropsychiatric disorders.ConclusionThe DYT1 variants described in this work represent exciting new targets for future studies designed to increase our understanding of the pathophysiology and pathogenesis of DYT1 dystonia.

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