Falcarindiol Purified From Carrots Leads to Elevated Levels of Lipid Droplets and Upregulation of Peroxisome Proliferator-Activated Receptor-γ Gene Expression in Cellular Models

Camilla Bertel Andersen; Anders Runge Walther; Emma Pipó-Ollé; Martine K Notabi; Sebastian Juul; Mathias Hessellund Eriksen; Adam Leslie Lovatt; Richard Cowie; Jes Linnet; Morten Kobaek-Larsen; Rime El-Houri; Morten Østergaard Andersen; Martin Aage Barsøe Hedegaard; Lars Porskjær Christensen; Eva Christensen Arnspang

doi:10.3389/fphar.2020.565524

Falcarindiol Purified From Carrots Leads to Elevated Levels of Lipid Droplets and Upregulation of Peroxisome Proliferator-Activated Receptor-γ Gene Expression in Cellular Models

Front Pharmacol. 2020 Aug 28:11:565524. doi: 10.3389/fphar.2020.565524. eCollection 2020.

Authors

Camilla Bertel Andersen¹, Anders Runge Walther^{1

2}, Emma Pipó-Ollé¹, Martine K Notabi¹, Sebastian Juul¹, Mathias Hessellund Eriksen¹, Adam Leslie Lovatt¹, Richard Cowie², Jes Linnet^{2

3}, Morten Kobaek-Larsen^{4

5}, Rime El-Houri¹, Morten Østergaard Andersen¹, Martin Aage Barsøe Hedegaard¹, Lars Porskjær Christensen⁶, Eva Christensen Arnspang¹

Affiliations

¹ Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark.
² The Maersk Mc-Kinney Moller Institute, University of Southern Denmark, Odense, Denmark.
³ Mads Clausen Institute, University of Southern Denmark, Odense, Denmark.
⁴ Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁵ Department of Surgery, Odense University Hospital, Odense, Denmark.
⁶ Department of Chemistry and Bioscience, Faculty of Engineering and Science, Aalborg University, Esbjerg, Denmark.

Abstract

Falcarindiol (FaDOH) is a cytotoxic and anti-inflammatory polyacetylenic oxylipin found in food plants of the carrot family (Apiaceae). FaDOH has been shown to activate PPARγ and to increase the expression of the cholesterol transporter ABCA1 in cells, both of which play an important role in lipid metabolism. Thus, a common mechanism of action of the anticancer and antidiabetic properties of FaDOH may be due to a possible effect on lipid metabolism. In this study, the effect of sub-toxic concentration (5 μM) of FaDOH inside human mesenchymal stem cells (hMSCs) was studied using white light microscopy and Raman imaging. Our results show that FaDOH increases lipid content in the hMSCs cells as well as the number of lipid droplets (LDs) and that this can be explained by increased expression of PPARγ2 as shown in human colon adenocarcinoma cells. Activation of PPARγ can lead to increased expression of ABCA1. We demonstrate that ABCA1 is upregulated in colorectal neoplastic rat tissue, which indicates a possible role of this transporter in the redistribution of lipids and increased formation of LDs in cancer cells that may lead to endoplasmic reticulum stress and cancer cell death.

Keywords: ABCA1; PPARγ; Raman spectroscopy; cholesteryl esters; colorectal cancer; falcarindiol; lipid droplets; type 2 diabetes.