Anthocyanin oligomers stimulate browning in 3T3‐L1 white adipocytes via activation of the β3‐adrenergic receptor and ERK signaling pathway

Abstract

Microbial fermentation of grape-skin extracts is found to synthesize anthocyanin oligomers (AO), which are more active than the monomeric anthocyanins that are effective for some metabolic diseases such as diabetes and obesity. This study investigated the functional role of AO in 3T3-L1 white adipocyte metabolism, with a focus on inducing browning. To achieve this, we determined the expressions of core genes and protein markers responsible for browning and lipid metabolism in response to AO treatment of 3T3-L1 white adipocytes. AO exposure significantly increases the expressions of beige-specific genes (Cidea, Cited1, Ppargc1α, Prdm16, Tbx1, Tmem26, and Ucp1) and brown-fat signature proteins (UCP1, PRDM16, and PGC-1α), and suppresses the expressions of lipogenic marker proteins while enhancing the protein levels of lipolysis in white adipocytes. The mechanistic study revealed stimulation of white fat browning via activation of the β3-AR/PKA/p38 axis and ERK/CREB signaling pathway subsequent to AO treatment. In conclusion, our current findings indicate the beneficial effects of AO for the treatment of obesity with interesting properties such as regulating the browning of adipocytes and increasing thermogenic activity.Although further research based on animal models or clinical trials remains, AO treatment can bring more insights into the treatment of obesity and metabolic syndrome.

Inhibition of Lipid Accumulation and Adipokine Levels in Maturing Adipocytes by Bauhinia rufescens (Lam.) Stem Bark Extract Loaded Titanium Oxide Nanoparticles

“…Kang et al [ 52 ] observed that punicalagin had decreased the levels of the Nf-κb signaling pathway associated with the inhibition of obesity-related inflammatory response. It was acknowledged that the proanthocyanidins in grape seeds stimulated long-term lipolysis by the activation of the β3-adrenergic receptor and the ERK signaling pathway, which increased cAMP and PKA in 3T3-L1 adipocytes [ 53 ].…”

Red foxtail millet upregulates brain-derived neurotrophic factor levels in vitro and in vivo

“…Moreover, the anthocyanin present in black rice activates PI3K/ Akt signaling in C2C12 myotubes (Feng et al, 2022). In addition, anthocyanin oligomers reportedly activate PKA and ERK/CREB signaling pathways in 3T3-L1 white adipocytes (Choi et al, 2021). Those anthocyanins that activate BDNF gene expression might be present in the butanol fraction of RFM.…”

Anthocyanin Oligomers Induce Apoptosis and Autophagy by Inhibiting the mTOR Signaling Pathway in Human Breast Cancer Cells

“…Several studies have reported that the anti-cancer effects of natural anthocyanins on breast cancer cells are due to reduced viability via cytotoxicity [ 11 , 12 ]. Moreover, oligomeric anthocyanins are known to possess higher biological activity compared to monomeric anthocyanins [ 7 , 10 , 13 ]. Consistent with these findings, we found that a synthetic AO effectively reduced the cell viability of breast cancer cells compared to delphinidin (a monomeric anthocyanin) ( Figure 1 B,C).…”

“…According to a previous study, an AO produced by the Aspergillus niger -based fermentation of grape skin extract was more biologically active than the monomeric anthocyanin ( Figure 1 A) [ 7 ]. Furthermore, it has been reported that the antioxidant activity of this AO mixture improved symptoms in a mouse model of dry eye disease and promoted the browning of white adipocytes by increasing fat metabolism [ 8 , 9 , 10 ]. However, though much research has been conducted on the anti-cancer effects of plant-sourced AOs, comparatively little is known about the anti-cancer effects of AOs synthesized by fermentation.…”