Phenolic Compounds Reduce the Fat Content in Caenorhabditis elegans by Affecting Lipogenesis, Lipolysis, and Different Stress Responses.

Paula Aranaz,Miguel López-Yoldi,Fermín I Milagro,Carlos J González-Navarro,David Navarro-Herrera,Ana Romo-Hualde,María Zabala,José Luis Vizmanos

doi:10.3390/ph13110355

Abstract

Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin, and epicatechin) and phenolic acids (p-coumaric, ellagic, ferulic, gallic, and vanillic acids) regulating C. elegans fat accumulation. Resveratrol exhibited the strongest lipid-reducing activity, which was accompanied by the improvement of lifespan, oxidative stress, and aging, without affecting worm development. Whole-genome expression microarrays demonstrated that resveratrol affected fat mobilization, fatty acid metabolism, and unfolded protein response of the endoplasmic reticulum (UPRER), mimicking the response to calorie restriction. Apigenin induced the oxidative stress response and lipid mobilization, while vanillic acid affected the unfolded-protein response in ER. In summary, our data demonstrates that phenolic compounds exert a lipid-reducing activity in C. elegans through different biological processes and signaling pathways, including those related with lipid mobilization and fatty acid metabolism, oxidative stress, aging, and UPR-ER response. These findings open the door to the possibility of combining them in order to achieve complementary activity against obesity-related disorders.

Highlights

Obesity is characterized by a misbalance between food intake and energy consumption, which leads to an excess of fat accumulation and an increased body weight [1]
In C. elegans, more than 400 genes involved in fat storage are evolutionarily conserved with mammals and act in common cellular pathways [14], constituting a convenient in vivo model for the screening of the effects of nutritional perturbations and the fatty acid modulation activity of bioactive components of the diet [11,17]
Whole-genome expression analyses demonstrate that this activity is mediated by changes in the expression of genes involved in lipid synthesis, oxidation, and mobilization, and involves other crucial biological processes, such as the cellular response to oxidative stress and unfolded protein response of the endoplasmic reticulum (UPRER), evidencing the importance of these processes in metabolism

Summary

Introduction

Obesity is characterized by a misbalance between food intake and energy consumption, which leads to an excess of fat accumulation and an increased body weight [1]. Different strategies have been suggested to reduce the excessive accumulation of fat characteristic of obesity In this sense, the identification and characterization of bioactive compounds (BACs) capable of regulating energy homeostasis represent a potential tool for the management and prevention of obesity-related diseases [4,5,6]. The identification and characterization of bioactive compounds (BACs) capable of regulating energy homeostasis represent a potential tool for the management and prevention of obesity-related diseases [4,5,6] Among these compounds, polyphenols and phenolic acids have been widely described to exert different beneficial and healthy properties, mainly attributed to their antioxidant and antiaging activities [7,8,9,10]. In order to be considered as potential agents against metabolic syndrome, more research is needed to elucidate and characterize the biological processes and mechanisms involved in this regulation

Objectives

Methods

Results

Conclusion