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Physiology and Biochemistry

Lampaya Medicinalis Phil. decreases lipid-induced triglyceride accumulation and proinflammatory markers in human hepatocytes and fat body of Drosophila melanogaster

International Journal of Obesity volume 45, pages 1464–1475 (2021)Cite this article

Subjects

Abstract

Background

Excess hepatic triglyceride (TG) accumulation (steatosis) commonly observed in obesity, may lead to non-alcoholic fatty liver disease (NAFLD). Altered regulation of intracellular lipid droplets (LD) and TG metabolism, as well as activation of JNK-mediated proinflammatory pathways may trigger liver steatosis-related disorders. Drosophila melanogaster is an animal model used for studying obesity and its associated disorders. In Drosophila, lipids and glycogen are stored in the fat body (FB), which resembles mammalian adipose tissue and liver. Dietary oversupply leads to obesity-related disorders, which are characterized by FB dysfunction. Infusions of Lampaya medicinalis Phil. (Verbenaceae) are used in folk medicine of Chile to counteract inflammatory diseases. Hydroethanolic extract of lampaya (HEL) contains considerable amounts of flavonoids that may explain its anti-inflammatory effect.

Methods

We studied whether HEL affects palmitic acid (PA, C16:0) and oleic acid (OA; C18:1)-induced TG accumulation and proinflammatory marker content in HepG2 hepatocytes as well as impaired lipid storage and proinflammatory molecule expression in Drosophila melanogaster fed a high-fat diet (HFD).

Results

In HepG2 hepatocytes, exposure to OA/PA elevated TG content, FABP4, ATGL and DGAT2 expression, and the JNK proinflammatory pathway, as well as TNF-α and IL-6 production, while diminished FAS expression. These effects were prevented by HEL co-treatment. In Drosophila larvae fed a HFD, HEL prevented TG accumulation and downregulated proinflammatory JNK pathway activation.

Conclusion

HEL effect counteracting OA/PA- and HFD-induced lipid accumulation and proinflammatory marker expression in HepG2 hepatocytes and Drosophila larvae may represent a preventive approach against hepatic steatosis and inflammation, associated to obesity and NAFLD.

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Fig. 1: HEL does not affect cell viability and ameliorates triglyceride content induced by OA/PA in HepG2 hepatocytes.
Fig. 2: Co-incubation with HEL prevents OA/PA-induced FABP4 expression and counteracts altered ATGL expression in HepG2 hepatocytes.
Fig. 3: HEL restores OA/PA-altered expression of lipogenic enzymes in HepG2 hepatocytes.
Fig. 4: Co-incubation with HEL prevents OA/PA-induced JNK phosphorylation and proinflammatory cytokine upregulation in HepG2 hepatocytes.
Fig. 5: HEL ameliorates triglyceride content induced by high-fat diet in fat body cells.
Fig. 6: HEL counteracts the effect of HFD on proinflammatory marker expression.

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Acknowledgements

The authors are thankful to Prof Dr. Roberto Rodriguez, Universidad de Concepción, Chile for authentication of the plant material. We thank Cecilia Fuentes from OMEGA Laboratory of the Institute of Nutrition and Food Technology for her technical assistance.

Funding

This work was supported by funding from SOCHED (N°2018–03) and SOCHINUT (N° 301) to PO, PAI77170001 to NT, Fondecyt 1150651 to MC, Network for Extreme Environments Research project, Universidad de Antofagasta (NEXER; Project ANT1756) to GM and AP.

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Authors and Affiliations

  1. Institute of Health Sciences, Universidad de O’Higgins, Av. Libertador Bernardo O’Higgins 611, 2820000, Rancagua, Chile

    Sofía Sanhueza, Karin Herrera & Paulina Ormazabal

  2. Laboratory of Obesity and Metabolism in Geriatrics and Adults (OMEGA), Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Av. El Líbano 5524, 7830490, Macul, Santiago, Chile

    Sofía Sanhueza, Mariana Cifuentes, Karin Herrera & Paulina Ormazabal

  3. Cellular and Molecular Biology Laboratory, Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Av. El Líbano 5524, 7830490, Macul, Santiago, Chile

    Nicolás Tobar & Daniela Quenti

  4. Center for Gender-Specific Medicine, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy

    Rosaria Varì, Beatrice Scazzocchio & Roberta Masella

  5. Laboratorio de Química Biológica, Instituto Antofagasta (IA) and Departamento de Química, Facultad de Ciencias Básicas, Universidad de Antofagasta, Av. Angamos 601, 1240000, Antofagasta, Chile

    Adrián Paredes & Glauco Morales

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Contributions

Conceptualization, PO; methodology, PO, SS, RV, BS, KH, MC, NT, AP, and GM; investigation, SS, RV, BS, KH, DQ, NT, and AP; formal analysis, PO, NT, and MC; resources, PO, MC, NT, RM, AP, and GM; writing—original draft preparation, PO, SS, and NT; writing—review and editing, MC, RM, and PO; supervision, PO.

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Correspondence to Paulina Ormazabal.

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Sanhueza, S., Tobar, N., Cifuentes, M. et al. Lampaya Medicinalis Phil. decreases lipid-induced triglyceride accumulation and proinflammatory markers in human hepatocytes and fat body of Drosophila melanogaster. Int J Obes 45, 1464–1475 (2021). https://doi.org/10.1038/s41366-021-00811-8

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