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Melatonin Modulates lipid Metabolism in HepG2 Cells Cultured in High Concentrations of Oleic Acid: AMPK Pathway Activation may Play an Important Role

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Abstract

Melatonin exists as an active ingredient in several foods and has been reported to inhibit fatty liver disease in animals; however, its molecular mechanisms are not well elucidated. Herein, we explored effects of melatonin on lipid accumulation induced by oleic acid in HepG2 cells and characterized the underlying molecular mechanisms. Pretreatment with melatonin (0.1–0.3 mM) significantly inhibited accumulation of triglyceride and cholesterol induced by incubating HepG2 cells with high concentrations of oleic acid (oleic acid overload) (p < 0.05). Melatonin pretreatment induced phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), causing their activation and inactivation, respectively. Expression levels of peroxisome proliferator activated receptor-α (PPARα) and its target gene carnitine palmitoyl-CoA transferase 1 (CPT1), which are associated with lipolysis, were upregulated by melatonin, whereas expression of sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD1), which are associated with lipogenesis, were downregulated. Melatonin did not change expression of genes involved in cholesterol metabolism, including 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) and SREBP-2. Melatonin inhibits lipid accumulation induced by oleic acid overload in HepG2 cells. The phosphorylation and activation of AMPK may have important roles in inactivating lipid anabolic pathways and activating triglyceride catabolic pathways.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 31570687).

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Author notes

  1. These authors are contributed equally: Yan Mi and Dehong Tan

  2. These authors jointly supervised this work: Yan Mi and Dehong Tan

Authors and Affiliations

  1. College of Food, Shenyang Agricultural University, No. 120 Dongling Road, Shenhe District, Shenyang City, 110866, China

    Yan Mi, Dehong Tan, Yin He, Xin Zhou, Qian Zhou & Shujuan Ji

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  1. Yan Mi
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  2. Dehong Tan
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  3. Yin He
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  4. Xin Zhou
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Correspondence to Shujuan Ji.

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Mi, Y., Tan, D., He, Y. et al. Melatonin Modulates lipid Metabolism in HepG2 Cells Cultured in High Concentrations of Oleic Acid: AMPK Pathway Activation may Play an Important Role. Cell Biochem Biophys 76, 463–470 (2018). https://doi.org/10.1007/s12013-018-0859-0

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  • DOI: https://doi.org/10.1007/s12013-018-0859-0

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