The Ability of Quercetin and Ferulic Acid to Lower Stored Fat is Dependent on the Metabolic Background of Human Adipocytes

Abstract

Scope: Dietary flavonoids and phenolic acids can modulate lipid metabolism, but effects on mature human adipocytes are not well characterized.

Materials and methods: Human adipocytes are differentiated, and contain accumulated lipids, mimicking white adipocytes. They are then cultured either under conditions of actively synthesizing and accumulating additional lipids through lipogenesis ("ongoing lipogenic state") or under conditions of maintaining but not increasing stored lipids ("lipid storage state"). Total lipid, lipidomic and transcriptomics analyses are employed to assess changes after treatment with quercetin and/or ferulic acid.

Results: In the "lipid storage state," a longer-term treatment (3 doses over 72 h) with low concentrations of quercetin and ferulic acid together significantly lowered stored lipid content, modified lipid composition, and modulated genes related to lipid metabolism with a strong implication of peroxisome proliferator-activated receptor (PPARα)/retinoid X receptor (RXRα) involvement. In the "ongoing lipogenic state," the effect of quercetin and ferulic acid is markedly different, with fewer changes in gene expression and lipid composition, and no detectable involvement of PPARα/RXRα, with a tenfold higher concentration required to attenuate stored lipid content.

Conclusions: Multiple low-dose treatment of quercetin and ferulic acid modulates lipid metabolism in adipocytes, but the effect is dramatically dependent on the metabolic state of the cell.

Keywords: Simpson-Golabi-Behmel syndrome; gene expression; lipogenesis; liver X receptors; nuclear receptors; retinoid X receptors.