Increasing cAMP levels of preadipocytes by cyanidin-3-glucoside treatment induces the formation of beige phenotypes in 3T3-L1 adipocytes

Abstract

Obesity is a serious health problem and a major risk factor for the onset of several diseases such as heart disease, diabetes, stroke and cancer. The conversion of white adipocytes to brown-like adipocytes, also called beige or brite adipocytes, by pharmacological and dietary compounds has gained attention as an effective treatment for obesity. Cyanidin-3-glucoside (Cy3G), a polyphenolic compound contained in black soybean, blueberry and grape, has several antiobesity effects. However, there are no reports on the role of Cy3G in the induction of differentiation of preadipocytes to beige adipocytes and corresponding phenotypes. Here, the formation of beige adipocyte phenotypes following treatment with Cy3G was evaluated using 3T3-L1 adipocytes. Cy3G induced phenotypic changes to white adipocytes, such as increased multilocular lipid droplets and mitochondrial content. Additionally, the expression of mitochondrial genes (TFAM, SOD2, UCP-1 and UCP-2), UCP-1 protein and beige adipocyte markers (CITED1 and TBX1) in 3T3-L1 adipocytes was increased by Cy3G. Furthermore, Cy3G promoted preadipocyte differentiation by up-regulating of C/EBPβ through the elevation of the intracellular cAMP levels. These results indicated that Cy3G elevates the intracellular cAMP levels, which induces beige adipocyte phenotypes. This is the first report on the effect of Cy3G on induction of differentiation of preadipocytes into beige adipocyte phenotypes.

Flavonoids, Potential Bioactive Compounds, and Non-Shivering Thermogenesis

“…Consistent with the results of studies performed with whole extracts of anthocyanin-rich-foods, the treatment of 3T3-L1 cells with 50 µM or 100 µM cyanidin-3-glucoside also converted 3T3-L1 preadipocytes to beige adipocytes during differentiation [ 97 ]. A cyanidin-3-glucoside-induced browning effect was possibly due to both reduced AMP/ATP level-induced AMPK activation and enhanced brown adipogenesis by cAMP-mediated C/EBPβ, a transcriptional factor that is involved in the adipogenesis induced PGC1α-UCP1 pathway [ 97 ]. The db/db mice that were administered drinking water containing cyanidin-3-glucoside (1 mg/mL) for 16 weeks showed beige cell formation in SWAT and increased BAT activity [ 98 ].…”

TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue

“…Beiging of scWAT has been shown to be orchestrated by various cell types residing within the white fat depot, including (pre-)adipocytes 49 – 51 , sympathetic neuronal fibres 52 , 53 and immune cells 54 – 56 . We characterised a mouse strain with a loss-of-function of TGR5 in adipocytes and performed comprehensive studies in 3T3-L1 and primary beige cells.…”

Blackberry Feeding Increases Fat Oxidation and Improves Insulin Sensitivity in Overweight and Obese Males

“…One possible explanation for the insulin sensitizing effect of berries is the activation of adenosine monophosphate protein kinase across several tissues involved in glucoregulation [ 16 , 48 ]. Furthermore, amelioration of fatty acid overload may be possible by the beige-adipocyte phenotype invoked by cyanidin-3-glucoside, thereby improving insulin signaling [ 49 ]. Other mechanistic work highlights the potential to inhibit adipogenic enzymes of the liver as well as reduce the absorption of glucose from the gut [ 8 , 50 ].…”