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Lauric acid alleviates insulin resistance by improving mitochondrial biogenesis in THP-1 macrophages

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Abstract

Mitochondrial dysfunction plays a crucial role in the central pathogenesis of insulin resistance and type 2 diabetes mellitus. Macrophages play important roles in the pathogenesis of insulin resistance. Lauric acid is a 12-carbon medium chain fatty acid (MCFA) found abundantly in coconut oil or palm kernel oil and it comes with multiple beneficial effects. This research objective was to uncover the effects of the lauric acid on glucose uptake, mitochondrial function and mitochondrial biogenesis in insulin-resistant macrophages. THP-1 monocytes were differentiated into macrophages and induce insulin resistance, before they were treated with increasing doses of lauric acid (5 μM, 10 μM, 20 μM, and 50 μM). Glucose uptake assay, cellular ROS and ATP production assays, mitochondrial content and membrane potential assay were carried out to analyse the effects of lauric acid on insulin resistance and mitochondrial biogenesis in the macrophages. Quantitative RT-PCR (qRT-PCR) and western blot analysis were also performed to determine the expression of the key regulators. Insulin-resistant macrophages showed lower glucose uptake, GLUT-1 and GLUT-3 expression, and increased hallmarks of mitochondrial dysfunction. Interestingly, lauric acid treatment upregulated glucose uptake, GLUT-1 and GLUT-3 expressions. The treatment also restored the mitochondrial biogenesis in the insulin-resistant macrophages by improving ATP production, oxygen consumption, mitochondrial content and potential, while it promoted the expression of mitochondrial biogenesis regulator genes such as TFAM, PGC-1α and PPAR-γ. We show here that lauric acid has the potential to improve insulin sensitivity and mitochondrial dysregulation in insulin-resistant macrophages.

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Acknowledgements

This work was supported by Malaysia’s Ministry of Higher Education’s Fundamental Research Grant Scheme (FRGS) (FRGS/1/2016/SKK06/UTAR/02/1).

Funding

This work was supported by Malaysia’s Ministry of Higher Education’s Fundamental Research Grant Scheme (FRGS) (FRGS/1/2016/SKK06/UTAR/02/1).

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Authors and Affiliations

  1. Department of Allied Health Sciences, Faculty of Science, Universiti Tunku Abdul Rahman, Jalan Universiti, Bandar Barat, 31900, Kampar, Perak, Malaysia

    Yong Yao Tham & Choy Hoong Chew

  2. Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman, Jalan Universiti, Bandar Barat, 31900, Kampar, Perak, Malaysia

    Quok Cheong Choo

  3. Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030, Kuala Terengganu, Nerus, Malaysia

    Tengku Sifzizul Tengku Muhammad

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  1. Yong Yao Tham
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  2. Quok Cheong Choo
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Contributions

YY Tham carried out the experiment and data analyses/interpretation, and wrote the manuscript. CH Chew was the principal investigator and contributed to the study design as well as interpretation of the findings. QC Choo and TM Tengku Muhammad were the co-investigators of the grants.

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Correspondence to Choy Hoong Chew.

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Tham, Y.Y., Choo, Q.C., Muhammad, T.S.T. et al. Lauric acid alleviates insulin resistance by improving mitochondrial biogenesis in THP-1 macrophages. Mol Biol Rep 47, 9595–9607 (2020). https://doi.org/10.1007/s11033-020-06019-9

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