The effects of persistent organic pollutant dioxin on reverse cholesterol transport pathway of hdl in differentiated 3t3-l1 adipocytes

Cardiovascular disease (CVD) the leading cause of mortality globally occurs primarily due to coronary artery disease caused by hypertension, diabetes and dyslipidemia. In addition to the above-mentioned risk factors, persistent organic pollutants (POPs) which include dioxin also play a role in CVD....

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Main Authors: Ali, Roslina, Abdul Rahman, Thuhairah Hasrah, Abd Muid, Suhaila, Salim, Norita, Ramzi, Ahmad, Hamimah, Siti, Razali, Ruzi Hamimi, Chainchel Singh, Mansharan Kaur
Format: Article
Language:en
Published: Research and Innovation Division, Universiti Teknologi MARA (UiTM) Selangor 2025
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Online Access:https://ir.uitm.edu.my/id/eprint/130335/1/130335.pdf
https://ir.uitm.edu.my/id/eprint/130335/
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Summary:Cardiovascular disease (CVD) the leading cause of mortality globally occurs primarily due to coronary artery disease caused by hypertension, diabetes and dyslipidemia. In addition to the above-mentioned risk factors, persistent organic pollutants (POPs) which include dioxin also play a role in CVD. They are transported by lipoproteins and accumulate in adipose tissue with low-density lipoprotein (LDL) found to be the main transporter of lipid-soluble POPs. However, very-LDL (VLDL) and high-density lipoprotein (HDL) have also been associated with lipid-soluble POPs in humans. An in-vitro study looking at the effects of dioxin in reverse cholesterol transport (RCT) of high-density lipoprotein cholesterol (HDL-c), an anti-atherogenesis pathway was undertaken to further understand it’s mechanism of action. MATERIALS AND METHOD: 3T3-L1 preadipocytes were differentiated into mature adipocytes according to manufacturer instructions. A cholesterol efflux capacity assay was performed using mature adipocytes loaded with fluorescence-labelled cholesterol and treated with dioxin concentrations of 1,10,30 nm and dioxin 30 nm together with rosiglitazone (0.005 μmol/ml). The movement of labelled cholesterol from the cells to the acceptor (HDL) was quantified with the intensity of fluorescence-labelled cholesterol measured at 485 nm excitation and 523 nm emission. RESULTS AND DISCUSSION: The percentage of cholesterol efflux using dioxin concentrations of 1 and 10 nm and HDL was lower than that of HDL alone. However, the highest Dioxin concentration (30 nm) showed comparable results with HDL after a 4 hours efflux incubation period. Dioxin together with rosiglitazone and HDL showed unexpected results with a lower percentage of cholesterol efflux. This shows that Dioxin and rosiglitazone did not significantly increase the ability of HDL to promote cholesterol efflux in mature adipocytes as it should function.