The Preliminary Evaluation of Epigenetic Modifications Regulating the Expression of IL10 in Insulin-Resistant Adipocytes

A higher level of IL10 expression in obesity and insulin resistance was observed in both human and mouse WAT. In our research, we analyzed the influence of insulin resistance on epigenetic modification within the promoter region IL10 gene and the potential influence of these modifications on its expression. Studies were performed using two cell models for the analysis: human, preadipocytes derived from adipose (visceral and subcutaneous) tissues and murine 3T3-L1 fibroblasts. We demonstrated a significant increase in the IL10 expression level, IL10 promoter region methylation, and histone 3 epigenetic modifications: H3K4me and H3K9/14ac, in insulin resistance cells (IR) from SAT cell culture. In IR cells from VAT cell culture, we observed decreased IL10 expression with a simultaneous increase of IL10 promoter region methylation. In IR cells from 3T3L1 cell culture, we observed the increased expression of IL10 as well as the decreased levels of methylation in the IL10 promoter region and histone methylation (H3K4me) and acetylation (H3K9/14ac). The presented analyses suggest a potential impact of epigenetic modifications on gene expression and a potential mutual influence of epigenetic modifications on each other or the activation of specific epigenetic regulation at a different stage of the development of insulin resistance in cells

Metabolic Differences between Subcutaneous and Visceral Adipocytes Differentiated with an Excess of Saturated and Monounsaturated Fatty Acids

Obesity is a major health problem in highly industrialized countries. High-fat diet (HFD) is one of the most common causes of obesity and obesity-related disorders. There are considerable differences between fat depots and the corresponding risks of metabolic disorders. We investigated the various effects of an excess of fatty acids (palmitic 16:0, stearic 18:0, and oleic acids 18:1n−9) on adipogenesis of subcutaneous- and visceral-derived mesenchymal stem cells (MSCs) and phenotypes of mature adipocytes. MSCs of white adipose tissue were acquired from adipose tissue biopsies obtained from subcutaneous and visceral fat depots from patients undergoing abdominal surgery. The MSCs were extracted and differentiated in vitro with the addition of fatty acids. Oleic acid stimulated adipogenesis, resulting in higher lipid content and larger adipocytes. Furthermore, oleic acid stimulated adipogenesis by increasing the expression of CCAAT enhancer binding protein β (CEBPB) and peroxisome proliferator activated receptor γ (PPARG). All of the examined fatty acids attenuated the insulin-signaling pathway and radically reduced glucose uptake following insulin stimulation. Visceral adipose tissue was shown to be more prone to generate inflammatory stages. The subcutaneous adipose tissue secreted a greater quantity of adipokines. To summarize, oleic acid showed the strongest effect on adipogenesis. Furthermore, all of the examined fatty acids attenuated insulin signaling and secretion of cytokines and adipokines

<i>Cornus mas</i> L. Increases Glucose Uptake and the Expression of <i>PPARG</i> in Insulin-Resistant Adipocytes

Cornus mas L., also known as cornelian cherry (CM), is a species that has long been cultivated in many different countries. In numerous scientific reports, cornelian cherry is used to treat numerous diseases and conditions. The presented study evaluated the effect of red and yellow Cornus mas L. extract on insulin sensitivity in adipocytes. 3T3-L1 fibroblasts as well as human SAT-derived and VAT-derived adipocytes were differentiated in vitro, and insulin resistance was induced using palmitic acid (16:0). The effect of CM fruit extract was analyzed in terms of glucose uptake and insulin signaling gene expression. In the glucose uptake test after insulin stimulation, a significant increase in glucose uptake was demonstrated in cells treated with CM fruit extracts. Furthermore, CM fruit extracts increased the expression of insulin signaling genes in adipocytes stimulated with insulin in control cells and adipocytes treated with CM extract. Additionally, a significant increase in peroxisome proliferator activated receptor gamma (PPARG) expression was observed in cells supplemented with CM extract. In conclusion, studies have shown that CM fruits can overcome insulin resistance and thus they have a positive effect on cell metabolism