Phenolic Compounds Inhibit 3T3-L1 Adipogenesis Depending on the Stage of Differentiation and Their Binding Affinity to PPARγ

Abstract

Phenolic compounds might modulate adiposity. Here, we report our observation that polyphenols and phenolic acids inhibit adipogenesis in 3T3-L1 with different intensity depending on the family and the stage of differentiation. While quercetin and resveratrol inhibited lipid accumulation along the whole process of differentiation, apigenin and myricetin were active during the early and latest stages, but not intermediate, contrary to hesperidin. The activity of phenolic acids was limited to the early stages of the differentiation process, except p-coumaric and ellagic acids. This anti-adipogenic effect was accompanied by down-regulation of Scd1 and Lpl. Molecular docking analysis revealed that the inhibitory activity of these phenolic compounds over the early stages of adipogenesis exhibits a significant correlation (r = 0.7034; p = 0.005) with their binding affinity to the ligand-binding domain of PPARγ. Results show that polyphenols and phenolic acids would interact with specific residues of the receptor, which could determine their potential anti-adipogenic activity during the early stages of the differentiation. Residues Phe264, His266, Ile281, Cys285 and Met348 are the most frequently involved in these interactions, which might suggest a crucial role for these amino acids modulating the activity of the receptor. These data contribute to elucidate the possible mechanisms of phenolic compounds in the control of adipogenesis.

Phenolic Compounds with Antioxidant Properties from Canola Meal Extracts Inhibit Adipogenesis

“…The TPC of various extracts in decreasing order was as follows: AE > BE > ME > EE > WE > CE > HE (Figure 1). to bind with particular residues (Phe264, His266, Ile281, Cys285, and Met348) of the PPARγ receptor to establish anti-adipogenicity during the early stages of the differentiation [29]. For example, ethanol extracts of bamboo stems have been shown to play a vital role in the downregulation of differentiation markers C/EBPβ, PPARγ, and FABP4 (fatty acid-binding protein) [30].…”

“…Sinapic acid [27], and hydroxycinnamic acids [28] are known for the lipolysis and their role in anti-adipogenesis. Polyphenols including quercetin, resveratrol, apigenin, and myricetin are known to bind with particular residues (Phe264, His266, Ile281, Cys285, and Met348) of the PPARγ receptor to establish anti-adipogenicity during the early stages of the differentiation [29]. For example, ethanol extracts of bamboo stems have been shown to play a vital role in the downregulation of differentiation markers C/EBPβ, PPARγ, and FABP4 (fatty acid-binding protein) [30].…”

Stearoyl-CoA Desaturase-1 Enzyme Inhibition by Grape Skin Extracts Affects Membrane Fluidity in Human Colon Cancer Cell Lines

“…Furthermore, there are molecules that induce apoptosis in different types of cancer by acting specifically on SCD1 [14]. The inhibition of SCD1 through natural compounds can result in health benefits [16][17][18]. The sterculic oil is an extremely precious natural product, capable of inhibiting SCD1 enzyme in obese ob/ob mice, reducing fat accumulation in the liver and adipose tissue and improving inflammation and insulin resistance, factors that create an environment conducive to the development of cancer [17].…”

Anti-osteoporotic and Anti-adipogenic Effects of Rhus chinensis Nutgalls in Ovariectomized Mice Fed with a High-fat Diet

“…Besides anti-osteoporotic activities, the phenolic fractions and gallotannins, including penta-O-galloyl-β-D-glucose from NRCs, have been shown to inhibit pancreatic lipase activity involved in fat absorption [11,34]. It has also been shown that phenolic acids (ellagic acid and gallic acid), flavonoids (kaempferol, quercetin, and luteolin), and penta-O-galloyl-β-D-glucose inhibit adipocyte differentiation in 3T3-L1 pre-adipocytes [35][36][37]. In our adipocyte differentiation assay, penta-O-galloyl-β-D-glucose was found to inhibit the adipocyte differentiation of D1 cells at 10 µM (our unpublished data).…”