apolipoprotein a5
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2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Yu ◽  
Lina Yu ◽  
Nuo Cheng ◽  
Xiaoguang Liu ◽  
Chunlu Fang ◽  
...  

Background: Apolipoprotein A5 (ApoA5), an important modulator of plasma and hepatic triglyceride metabolism, has been found to be downregulated by metformin to improve non-alcoholic fatty liver disease. Meanwhile, exercise has been recommended as a therapeutic strategy for non-alcoholic steatohepatitis (NASH). However, no study has yet determined whether exercise affects hepatic ApoA5 expression or the inhibition of ApoA5 to toll-like receptor 4 (TLR4). We herein examined the effects of exercise on hepatic ApoA5 expression and the relevance of ApoA5 and TLR4-mediated pathway in mice with high-fat diet (HFD)-induced NASH.Methods: Male C57BL/6J mice were built NASH model with high-fat diet for 12 weeks, and following mice were subjected to exercise for 12 weeks on a treadmill. Microscopy and enzyme-linked immunosorbent assay were used to measure histological analysis of liver and hepatic lipids, respectively. Quantitative real-time PCR and western blot were used to determined mRNA and protein levels of ApoA5 and TLR4-mediated nuclear factor kappa B (NF-κB) pathway components, respectively. ApoA5 overexpression plasmids transfected into mice to investigate the relevance of ApoA5 and TLR4.Results: 12 weeks of exercise remarkably alleviated HFD-induced hepatic lipid accumulation, inflammation, and fibrosis, as well as reduced serum lipopolysaccharide (LPS), hepatic TLR4, myeloid differentiation factor 88 (MyD88), and NF-κBp65 expression. Importantly, exercise did not reduce ApoA5 expression but instead enhanced its ability to suppress TLR4-mediated NF-κB pathway components by decreasing circulating LPS in our experiments involving transfection of ApoA5 overexpression plasmids and LPS interventions.Conclusion: The results demonstrated that exercise improved HFD-induced NASH by triggering the inhibitory effects of ApoA5 on the TLR4-mediated NF-κB pathway.


2021 ◽  
Vol 14 (3) ◽  
pp. 1695-1706
Author(s):  
Pratik P. Durgawale ◽  
Kailas D. Datkhile ◽  
Virendra C. Patil ◽  
Vasant V. Devkar ◽  
Sarjerao A. Dabane ◽  
...  

The most commonly found type of diabetes in India is type II diabetes mellitus (T2DM), which is characterized by decrease in insulin secretion and decrease in insulin sensitivity. Several environmental factors, genetic factors, socio-economic factors, life style, dietary habits have contributed to the surge of T2DM cases in India. Numerous genes involved in lipid metabolism are likely to be candidates as the markers for obesity and T2DM. In the present study, single nucleotide polymorphism (SNP) of two genes namely Apolipoprotein A5 (APOA5) and Lipoprotein lipase (LPL) involved in triglyceride metabolism were investigated using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). The control group comprised of non-obese, non-diabetic subjects (n=120) and T2DM cases were divided into obese (n=120), and non-obese (n=120) groups based on their body mass index (BMI). The demographic features between the control and cases were compared using Chi-square distribution. The genotype frequencies of control and cases were compared using analysis of variance (ANOVA) and binary logistic regression analysis (Odds’ ratio (OR) and adjusted Odds’ ratio). It was observed that APOA5 rs3135506 (OR = 0.46 (0.27-0.79); p = 0.007) was negatively associated, while APOA5 rs662799 (OR = 2.22 (1.28-3.84); p = 0.006) was significantly associated in non-obese diabetic patients. APOA5 rs3135506 (OR = 0.03 (0.01-0.06); p < 0.001) was negatively associated and rs662799 (OR = 4.68 (1.47-14.93); p = 0.01) was significantly associated in obese diabetic patients. Both LPL SNPs (rs285 and rs320) were found not to be associated with T2DM. The association of Apo A5 variants with T2DM may be because of post transcriptional inhibition leading to reduced Apo A5 expression or these alleles may be in linkage disequilibrium with alleles which directly affect the functioning of APOA5. The observations indicated that T2DM is a multi-factorial disease with a large number of gene-gene and gene-environment interactions.


2021 ◽  
Vol 141 ◽  
pp. 111803
Author(s):  
Rong Li ◽  
Wenqiang Zhu ◽  
Piaopiao Huang ◽  
Yang Yang ◽  
Fei Luo ◽  
...  

2021 ◽  
Author(s):  
Rong Li ◽  
Wenqiang Zhu ◽  
Piaopiao Huang ◽  
Yang Yang ◽  
Fei Luo ◽  
...  

ABSTRACTThe antipsychotic drug olanzapine was reported to induce nonalcoholic fatty liver disease (NAFLD), whereas the underlying mechanism remains incompletely understood. This study investigated whether apolipoprotein A5 (apoA5) and sortilin, two interactive factors involved in NAFLD pathogenesis, are implicated in olanzapine-induced NAFLD. In the present study, at week 8, olanzapine treatment successfully induced hepatic steatosis in male C57 BL/6J mice, even when fed a normal chow diet, which was independent of animal body weight gain. Likewise, olanzapine effectively mediated hepatocyte steatosis in human HepG2 cells in vitro, characterized by substantially elevated intracellular lipid droplets. Increased plasma triglyceride concentration and decreased plasma apoA5 levels were observed in mice treated for 8 weeks with olanzapine. Surprisingly, olanzapine markedly enhanced hepatic apoA5 protein levels in mice, without a significant effect on rodent hepatic ApoA5 mRNA expression. Our in vitro study showed that olanzapine reduced apoA5 protein levels in the medium and enhanced apoA5 protein expression in hepatocytes, whereas this drug exerted no effect on hepatocyte APOA5 mRNA expression. By transfecting APOA5 siRNA into HepG2 cells, it was demonstrated that APOA5 knockdown effectively reversed olanzapine-induced hepatocyte steatosis. In addition, olanzapine drastically increased sortilin mRNA and protein levels in vivo and in vitro. Interestingly, SORT1 knockdown reduced intracellular apoA5 protein expression and increased medium apoA5 protein levels in vitro, without affecting intracellular APOA5 mRNA expression. Furthermore, SORT1 knockdown greatly ameliorated hepatocyte steatosis in vitro. This study provides the first evidence that sortilin inhibits the hepatic apoA5 secretion that is attributable to olanzapine-induced NAFLD, which provides new insight into effective strategies against NAFLD for patients with schizophrenia administered olanzapine.


2021 ◽  
Author(s):  
Xiansheng Huang ◽  
Yiqi Zhang ◽  
Wenqiang Zhu ◽  
Piaopiao Huang ◽  
Jingmei Xiao ◽  
...  

Olanzapine, an antipsychotic drug, was reported to induce hypertriglyceridemia, whereas the underlying mechanism remains incompletely understood. This study was to determine the role of apolipoprotein A5 (apoA5) in olanzapine-induced hypertriglyceridemia. In this study, 36 drug-naive and first-episode schizophrenic adult patients (aged 18-60 years) in a multi-center clinical trial (ClinicalTrials.gov NCT03451734) were enrolled. Before and after olanzapine treatment, plasma lipid and apoA5 levels were detected. Moreover, 21 female C57BL/6 J mice (8 weeks old) were divided into 3 groups (n = 7/each group): low-dose olanzapine (3 mg/kg/day), high-dose olanzapine (6 mg/kg/day) and control group. After 6 weeks, plasma glucose, lipids and apoA5 as well as hepatic apoA5 protein and mRNA expression in these animals were detected. In our study in vitro, primary mouse hepatocytes and HepG2 cells were treated with olanzapine of 25, 50, 100 μmol/L, respectively. After 24 hours, apoA5 protein and mRNA levels in hepatocytes were detected. Our study showed that olanzapine treatment significantly increased plasma triglyceride levels and decreased plasma apoA5 levels in these schizophrenic patients. A significant negative correlation was indicated between plasma triglyceride and apoA5 levels in these patients. Consistently, olanzapine dose-dependently increased plasma triglyceride levels and decreased plasma apoA5 levels in mice. Surprisingly, an elevation of hepatic apoA5 protein levels was detected in mice after olanzapine treatment, with no changes of APOA5 mRNA expression. Likewise, olanzapine increased apoA5 protein levels in hepatocytes in vitro, without changes of hepatocyte APOA5 mRNA. Therefore, our study provides the first evidence about the role of apoA5 in olanzapine-induced hypertriglyceridemia. Furthermore, plasma apoA5 reduction, resulting in hypertriglyceridemia, could be attributed to olanzapine-induced inhibition of hepatic apoA5 secretion.


2021 ◽  
pp. 100068
Author(s):  
Yan Q. Chen ◽  
Thomas G. Pottanat ◽  
Eugene Y. Zhen ◽  
Robert W. Siegel ◽  
Mariam Ehsani ◽  
...  
Keyword(s):  

Author(s):  
Claudia Ress ◽  
Jochen Dobner ◽  
Kerstin Rufinatscha ◽  
Bart Staels ◽  
Maximilian Hofer ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Imane Morjane ◽  
Hicham Charoute ◽  
Sanaa Ouatou ◽  
Lamiae Elkhattabi ◽  
Houda Benrahma ◽  
...  

Purpose. Coronary artery diseases (CAD) are clinical cardiovascular events associated with dyslipidemia in common. The interaction between environmental and genetic factors can be responsible for CAD. The present paper aimed to examine the association between c.56C > G (rs3135506) APOA5 gene polymorphism and CAD in Moroccan individuals and to perform an association update meta-analysis. Materials and Methods. The c.56C > G variant was genotyped in 122 patients with CAD and 134 unrelated controls. Genetic association analysis and comparison of biochemical parameters were performed using R statistical language. In addition, a comprehensive meta-analysis including eleven published studies in addition to our case-control study results was conducted using Review Manager 5.3. Publication bias was examined by Egger’s test and funnel plot. Results. The case-control study data showed that the c.56C > G polymorphism was associated with CAD susceptibility under codominant (P-value = 0.001), recessive (P-value <0.001) and log-additive (P-value = 0.008) inheritance models. In addition, this polymorphism was significantly associated with increased levels of systolic and diastolic blood pressures, triglycerides, glycemia, and total cholesterol. Furthermore, meta-analysis showed a significant association between the c.56C > G gene polymorphism and increased risk of CAD under recessive (OR = 3.39[1.77–6.50], P value <0.001) and homozygote codominant (OR = 3.96[2.44–6.45], P value <0.001) models. Conclusion. Our case-control study revealed a significant association between c.56C > G polymorphism and CAD in the Moroccan population. In addition, meta-analysis data supported the implication of this polymorphism in CAD susceptibility.


2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Meriem Hechmi ◽  
Hamza Dallali ◽  
Meriem Gharbi ◽  
Haifa Jmel ◽  
Meriem Fassatoui ◽  
...  

Abstract Apolipoprotein A5 (APOA5) has been linked to metabolic syndrome (MetS) in several populations. In North Africa, only the Tunisian and Moroccan populations were investigated. Our aim is to assess the association between APOA5 gene variant (rs662799) and haplotypes with MetS in Tunisian population and to perform a meta-analysis in North Africa. A total of 594 Tunisian participants were genotyped for polymorphism rs662799 using KASPar technology. Two polymorphisms rs3135506 and rs651821 in APOA5 gene genotyped in our previous study, were used in addition to rs662799 to assess the haplotype association with MetS. The genotype of 875 participants was used for the meta-analysis. Statistical analyses were performed with R software. The rs662799 increases the risk of MetS under the dominant (P=0.018) and the additive models (P=0.028) in the Tunisian population. After stratification of the cohort following the sex and the geographic origin, a positive association of rs662799 with MetS was found for participant from the Northern region and for the women group. Only the haplotype AGT showed a significant association with MetS by decreasing the risk of the disease. The meta-analysis reported a significant association of rs662799 and rs3135506 with MetS. Our results showed a significant association between the APOA5 gene variants rs662799 and haplotypes with MetS and its traits in Tunisia. An impact of the sex and the geographic origin on the genotype distribution was highlighted. Our funding emphasizes the role of APOA5 in the development of MetS in North Africa.


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