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

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.

Grifola frondosa (Maitake) Extract Reduces Fat Accumulation and Improves Health Span in C. elegans through the DAF-16/FOXO and SKN-1/NRF2 Signalling Pathways

“…Nile Red (a dye for neutral lipids-#N3013, Sigma-Aldrich, USA) staining was performed as previously described [27,28,30], with minor modifications. Briefly, L4 worms were harvested in 1.5 mL tubes and washed two times with PBST (0.01% of Triton X-100 in phosphate-buffered saline).…”

“…ORO staining was performed as previously described [30,31]. The day before the staining of the worms, a fresh ORO solution was prepared by diluting stock (0.5% ORO in isopropanol) to a 60% solution with water, filtering (0.45 µM filter), stirring at room temperature overnight, and filtering again just before use.…”

“…As a fat reduction control, Orlistat-supplemented plates (6 µg/mL Orlistat; Sigma-Aldrich, St. Louis, MO, USA) were used [27,29]. The media was supplemented as previously described in [30], with some modifications. Grifola frondosa extracts were dissolved in ultrapure water and tested at concentrations of 10 and 20 µg/mL.…”

“…The fluorescent dye dihydroethidium (DHE; Dihydroethidium BioReagent, ≥95% (HPCE), Sigma-Aldrich, USA) was used to measure the in vivo levels of ROS as previously described [30,32,33]. Briefly, synchronized 500 L1 larvae were transferred onto plates containing water (control) or GE (10 and 20 µg/mL), and were grown until the L4 stage, when worms were collected.…”

“…Absorbance at 260/280 nm in a NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific, Wilmington, DE, USA) was used to determine the concentration and purity of RNA. DNA-free RNA was obtained for all samples by treating 1000 ng of RNA with DNAse (Ambion™ DNase I, RNase-free; Thermo Fisher Scientific, Inc., Waltham, MA, USA) following the manufacturer's instructions and then reverse-transcribed into cDNA following the previously described protocol [30].…”