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AdipoRon Effect on Expression of Lipid Metabolism Genes in Cultured Human Primary Macrophages

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Abstract

Atherosclerosis is characterized by excessive uptake of cholesterol-rich low-density lipoprotein (LDL) by vascular wall macrophages. The macrophages are transformed into foam cells, lipids accumulate in the intima of arteries, atherosclerotic plaques arise, and cardiovascular diseases develop. Adiponectin is an adipose tissue adipokine and possess anti-atherogenic and anti-inflammatory activities, which are mediated by adiponectin binding to its receptors AdipoR1 and AdipoR2. To exert its anti-atherogenic effect, adiponectin may regulate the reverse cholesterol transport and prevent foam cells formation. The small-molecule adiponectin receptor agonist AdipoRon was assumed to modulate expression of reverse cholesterol transport and inflammation genes in human macrophages. Several AdipoRon concentrations (0, 5, 10, and 20 µM) were tested for effect on expression of the lipid metabolism genes ABCA1, ABCG1, APOA1, NR1H3 (LXRα), NR1H2 (LXRβ), PPARG, and ACAT1 and the inflammation genes IL6, TNFA, and TLR4 in cultured human primary macrophages and the THP-1 macrophage cell line. Cell viability was measured using the MTS assay. ABCA1, ABCG1, APOA1, NR1H3, NR1H2, PPARG, ACAT1, IL6, TNFA, and TLR4 mRNA levels in human primary macrophages were assessed by real-time PCR. The PPARG and ABCA1 relative mRNA levels were found to increase in human primary macrophages treated with 5 or 10 μM AdipoRon for 24 h. A higher AdipoR-on concentration (20 μM) was cytotoxic to macrophages, especially THP-1 cells. The effect of Adipo-Ron on human macrophages and potential adiponectin receptor agonists are of interest to study in view of the need to develop new approaches to atherosclerosis prevention and treatment.

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ACKNOWLEDGMENTS

We are grateful to S.V. Orlov, E.E. Larionova, and D.A. Tanyanskii (Institute of Experimental Medicine) for help in experiments with THP-1 cells and discussion of the results.

Funding

This work was supported by the state programs “Study of the Molecular and Cell Components of the Pathogenesis of Socially Important Disorders to Develop Methods for Their Early Diagnosis and Treatment” (project no. 121060200125-2, experiments on gene expression in primary macrophage cultures) and “Molecular Mechanisms Activating Lipoprotein Transport across the Endothelium at Various Stages of Atherogenesis” (project no. FGWG-2022-0003, experiments on THP-1 cell viability).

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  1. Konstantinov St. Petersburg Institute of Nuclear Physics, National Research Center “Kurchatov Institute”, 188300, Gatchina, Leningrad Oblast, Russia

    I. A. Pobozheva, K. V. Dracheva, S. N. Pchelina & V. V. Miroshnikova

  2. Pavlov First St. Petersburg State Medical University, 197022, St. Petersburg, Russia

    I. A. Pobozheva, K. V. Dracheva, S. N. Pchelina & V. V. Miroshnikova

  3. Institute of Experimental Medicine, 197376, St. Petersburg, Russia

    S. N. Pchelina

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  1. I. A. Pobozheva
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Correspondence to I. A. Pobozheva.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study. The study was approved by the local Ethics Committee at Pavlov First St. Petersburg State Medical University.

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Translated by T. Tkacheva

Abbreviations: CCD, cardiovascular disorder; CHD, coronary heart disease; LDL, low-density lipoprotein; LXRα and LXRβ, liver X receptors α and β; RXR, retinoid X receptor; PPARα and PPARγ, peroxisome proliferator-activated receptors α and γ; ABCA1 and ABCG1, ATP-binding cassette transporters A1 and G1; HDL, high-density lipoprotein; RCT, reverse cholesterol transport; AdipoR1 and AdipoR2, adiponectin receptors 1 and 2; APOA1, apolipoprotein A1; ACAT-1, acyl-CoA:cholesterol acyltransferase 1; TNFα, tumor necrosis factor α; IL-6, interleukin 6; TLR4, Toll-like receptor 4; PBS, phosphate-buffered saline; DMSO, dimethyl sulfoxide; FBS, fetal bovine serum.

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Pobozheva, I.A., Dracheva, K.V., Pchelina, S.N. et al. AdipoRon Effect on Expression of Lipid Metabolism Genes in Cultured Human Primary Macrophages. Mol Biol 57, 616–623 (2023). https://doi.org/10.1134/S0026893323040143

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