Kiwifruit supplementation increases the gene expression of ATP-binding cassette transporter A1 and Liver X receptor α in liver and intestine of hamsters fed with high-fat diet

2021 ◽  
pp. 1-10
Author(s):  
Saba Moradi ◽  
Heidar Tavilani ◽  
Massoud Saidijam ◽  
Mohammad Hashemnia ◽  
Asad Vaisi-Raygani
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Cholesterol Efflux ◽  
Liver X Receptor ◽  
Atp Binding ◽  
Chow Diet ◽  
High Fat ◽  
Abca1 Gene ◽  
Atp Binding Cassette Transporter ◽  
Liver X Receptor Α

BACKGROUND: Liver X receptor α (LXRα) and ATP-binding cassette transporter A1 (ABCA1) as a lipid transporter play an important role in cholesterol efflux from cells. OBJECTIVE: This study was aimed to determine the effect of kiwifruit supplementation on LXRα and ABCA1 gene expressions in liver and intestine of hamsters fed with high-fat diet (HFD). METHODS: 36 Golden Syrian male hamsters were divided into 6 groups (n = 6) including, group 1 received chow diet (control normal), group 2 and 3 received chow diet plus 1.86 and 3.73 g/kg kiwifruit, group 4 received HFD, group 5 and 6 received HFD plus 1.86 and 3.73 g/kg kiwifruit for 8 weeks. RESULTS: ABCA1 gene expression were significantly decreased in the liver (p <  0.01) and the intestine (p <  0.05) of HFD group compared with control normal. The gene expression levels of ABCA1 from liver and intestine were increased in HFD treated with kiwifruit compare to untreated HFD group (p <  0.05). LXRα gene expression of intestine was increased in all of the kiwifruit treated groups compared with untreated groups (p <  0.05). CONCLUSIONS: Consumption of kiwifruit in in hamsters receiving HFD can improve cholesterol efflux from liver and intestine by increase the gene expression of ABCA1 and LXRα.

scholarly journals SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR

2006 ◽  
Vol 400 (3) ◽  
pp. 485-491 ◽  
Author(s):  
Jenny Wong ◽  
Carmel M. Quinn ◽  
Andrew J. Brown
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Cholesterol Efflux ◽  
Statin Treatment ◽  
Atp Binding ◽  
Abca1 Gene ◽  
Atp Binding Cassette Transporter ◽  
Abca1 Expression ◽  
E Box

Cholesterol accumulation and removal are regulated by two different transcription factors. SREBP-2 (sterol-regulatory-element-binding protein-2) is best known to up-regulate genes involved in cholesterol biosynthesis and uptake, whereas LXR (liver X receptor) is best known for up-regulating cholesterol efflux genes. An important cholesterol efflux gene that is regulated by LXR is the ATP-binding cassette transporter, ABCA1 (ATP-binding cassette transporter-A1). We have previously shown that statin treatment down-regulated ABCA1 expression in human macrophages, probably by inhibiting synthesis of the LXR ligand 24(S),25-epoxycholesterol. However, it was subsequently reported that ABCA1 expression is down-regulated by SREBP-2 through binding of SREBP-2 to an E-box element in ABCA1's proximal promoter. As statin treatment induces SREBP-2 activation, this may provide an alternative explanation for the statin-mediated down-regulation of ABCA1. In the present study, we employed a set of CHO (Chinese-hamster ovary) mutant cell lines to investigate the role of SREBP-2 in the regulation of ABCA1. We observed increased ABCA1 mRNA levels in SREBP-2-overexpressing cells and decreased levels in cells lacking a functional SREBP-2 pathway, which were restored when the SREBP-2 pathway was reinstated. Moreover, ABCA1 gene expression was positively associated with synthesis of 24(S),25-epoxycholesterol in these cell lines. In studies using a human ABCA1 promoter reporter assay, mutation of the E-box motif had a similar response as the wild-type construct to either statin treatment or addition of 24(S),25-epoxycholesterol. By contrast, these responses were completely ablated when the DR4 element to which LXR binds was mutated. These results support the idea that 24(S),25-epoxycholesterol and statin treatment influence ABCA1 transcription via supply of an LXR ligand and not through an SREBP-2/E-box-related mechanism. In addition, our results indicate a critical role of SREBP-2 as a positive regulator of ABCA1 gene expression by enabling the generation of oxysterol ligands for LXR.

scholarly journals Dichlorodiphenyltrichloroethane Impairs Amyloid Beta Clearance by Decreasing Liver X Receptor α Expression

2021 ◽  
Vol 13 ◽  
Author(s):  
Dongmei Wu ◽  
Yang Hu ◽  
Min Song ◽  
Gongbo Li
Keyword(s):  
Amyloid Beta ◽  
Critical Role ◽  
Liver X Receptor ◽  
Dynamics Simulation ◽  
Atp Binding ◽  
Atp Binding Cassette Transporter ◽  
Liver X Receptor Α ◽  
Aβ Clearance ◽  
Atp Binding Cassette

Abnormal amyloid beta (Aβ) clearance is a distinctive pathological mechanism for Alzheimer’s disease (AD). ATP-binding cassette transporter A1 (ABCA1), which mediates the lipidation of apolipoprotein E, plays a critical role in Aβ clearance. As an environmental factor for AD, dichlorodiphenyltrichloroethane (DDT) can decrease ATP-binding cassette transporter A1 (ABCA1) expression and disrupt Aβ clearance. Liver X receptor α (LXRα) is an autoregulatory transcription factor for ABCA1 and a target of some environmental pollutants, such as organophosphate pesticides. In this study, we aimed to investigate whether DDT could affect Aβ clearance by targeting LXRα. The DDT-pretreated H4 human neuroglioma cells and immortalized astrocytes were incubated with exogenous Aβ to evaluate Aβ consumption. Meanwhile, cytotoxicity and LXRα expression were determined in the DDT-treated cells. Subsequently, the antagonism of DDT on LXRα agonist T0901317 was determined in vitro. The interaction between DDT and LXRα was predicted by molecular docking and molecular dynamics simulation technology. We observed that DDT could inhibit Aβ clearance and decrease the levels of LXRα mRNA and LXRα protein. Moreover, DDT is supposed to strongly bind to LXRα and exert antagonistic effects on LXRα. In conclusion, this study firstly presented that DDT could inhibit LXRα expression, which would contribute to Aβ clearance decline in vitro. It provides an experimental basis to search for potential therapeutic targets of AD.

scholarly journals A Maternal High Fat Diet Leads to Sex-Specific Programming of Mechanical Properties in Supraspinatus Tendons of Adult Rat Offspring

2021 ◽  
Vol 8 ◽  
Author(s):  
Scott M. Bolam ◽  
Vidit V. Satokar ◽  
Subhajit Konar ◽  
Brendan Coleman ◽  
Andrew Paul Monk ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Maternal Diet ◽  
Biomechanical Properties ◽  
Female Offspring ◽  
Male Offspring ◽  
Chow Diet ◽  
Adult Offspring ◽  
High Fat ◽  
The Impact

Background: Over half of women of reproductive age are now overweight or obese. The impact of maternal high-fat diet (HFD) is emerging as an important factor in the development and health of musculoskeletal tissues in offspring, however there is a paucity of evidence examining its effects on tendon. Alterations in the early life environment during critical periods of tendon growth therefore have the potential to influence tendon health that cross the lifespan. We hypothesised that a maternal HFD would alter biomechanical, morphological and gene expression profiles of adult offspring rotator cuff tendon.Materials and Methods: Female Sprague-Dawley rats were randomly assigned to either: control diet (CD; 10% kcal or 43 mg/g from fat) or HFD (45% kcal or 235 mg/g from fat) 14 days prior to mating and throughout pregnancy and lactation. Eight female and male offspring from each maternal diet group were weaned onto a standard chow diet and then culled at postnatal day 100 for tissue collection. Supraspinatus tendons were used for mechanical testing and histological assessment (cellularity, fibre organisation, nuclei shape) and tail tendons were collected for gene expression analysis.Results: A maternal HFD increased the elasticity (Young's Modulus) in the supraspinatus tendon of male offspring. Female offspring tendon biomechanical properties were not affected by maternal HFD. Gene expression of SCX and COL1A1 were reduced in male and female offspring of maternal HFD, respectively. Despite this, tendon histological organisation were similar between maternal diet groups in both sexes.Conclusion: An obesogenic diet during pregnancy increased tendon elasticity in male, but not female, offspring. This is the first study to demonstrate that maternal diet can modulate the biomechanical properties of offspring tendon. A maternal HFD may be an important factor in regulating adult offspring tendon homeostasis that may predispose offspring to developing tendinopathies and adverse tendon outcomes in later life.

scholarly journals Berberine Improves High-Fat Diet Induced Atherosclerosis and Hepatic Steatosis in Apoe-/-Mice by Down-Regulating PCSK9 via ERK1/2 Pathway

2020 ◽  
Author(s):  
Chun-Yan Ma ◽  
Xiao-Yun Shi ◽  
Ya-Ru Wu ◽  
Yue Zhang ◽  
Hui-Lin Qu ◽  
...  
Keyword(s):  
Western Blotting ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Density Lipoprotein ◽  
Atp Binding ◽  
Type I ◽  
High Fat ◽  
Atp Binding Cassette Transporter ◽  
Atp Binding Cassette

Abstract Background:Berberine (BBR) is a kind of alkaloid derived from Chinese herbal medicine, which has multiple pharmacological activities including anti-atherosclerosis (AS). However, the mechanism underlying the role of BBR in modulating lipid metabolic disorders is not fully clear. The aim of the present study was to investigate the beneficial effects of BBR on AS in ApoE-/- mice and its potential mechanisms.Methods: Eight-week old ApoE-/- mice with high-fat diet (HFD) and wild type mice were administered eitherBBR (50mg/kg/d and 100mg/kg/d, respectively) or equivoluminal saline. After the 16-week treatment, the blood was collected for lipid evaluation, and aorta and liver were obtained from the mice for hematoxylin-eosin (HE) staining, oil red O staining and Western blotting. HepG2 Cells were treated by BBR (0, 5, 25, and 50 μg/ml) for 24 hours. Real-time PCR or Western blotting was used to examine the expression levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), LDL receptor (LDLR), ATP-binding cassette transporter A1(ABCA1), ATP-binding cassette transporter G1(ABCG1) and scavenger receptor class B type I(SR-BI).Results: BBR significantly decreased serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) level in ApoE-/- mice fed with HFD. Moreover, BBR markedly reduced aorta atheroscleroticplaque, ameliorated lipid deposition in the liver in vivo. BBR could also promote intracellular cholesterol efflux and regulate LDLR and PCSK9 expression via the ERK1/2 pathway in HepG2 cells.Conclusions: BBR could improve lipid metabolism, decrease aorta AS and hepatic lipid accumulation in ApoE-/- mice fed with HFD, which was associated with down-regulation of PCSK9 through ERK1/2 pathway.

Sign in / Sign up

Export Citation Format

Share Document