Grape pomace extract induced beige cells in white adipose tissue from rats and in 3T3-L1 adipocytes

Abstract

This study investigated the effects of a grape pomace extract (GPE) rich in phenolic compounds on brown-like adipocyte induction and adiposity in spontaneously hypertensive (SHR) and control normotensive Wistar-Kyoto (WKY) rats fed a high-fat diet (HFD). HFD consumption for 10 weeks significantly increased epididymal white adipose tissue (eWAT) in WKY but not in SHR rats. Supplementation with GPE (300 mg/kg body weight/day) reduced adipocyte diameter and increased levels of proteins that participate in adipogenesis and angiogenesis, i.e., peroxisome-proliferator activated receptor gamma (PPARγ), vascular endothelial grow factor-A (VEGF-A) and its receptor 2 (VEGF-R2), and partially increased the uncoupling protein 1 (UCP-1) in WKY. In both strains, GPE attenuated adipose inflammation. In eWAT from SHR, GPE increased the expression of proteins involved in adipose tissue "browning," i.e., PPARγ-coactivator-1α (PGC-1α), PPARγ, PR domain containing 16 (PRDM16) and UCP-1. In primary cultures of SHR adipocytes, GPE-induced UCP-1 up-regulation was dependent on p38 and ERK activation. Accordingly, in 3T3-L1 adipocytes treated with palmitate, the addition of GPE (30 μM) activated the β-adrenergic signaling cascade (PKA, AMPK, p38, ERK). This led to the associated up-regulation of proteins involved in mitochondrial biogenesis (PGC-1α, PPARγ, PRDM16 and UCP-1) and fatty acid oxidation (ATGL). These effects were similar to those exerted by (-)-epicatechin and quercetin, major phenolic compounds in GPE. Overall, in HFD-fed rats, supplementation with GPE promoted brown-like cell formation in eWAT and diminished adipose dysfunction. Thus, winemaking residues, rich in bioactive compounds, could be useful to mitigate the adverse effects of HFD-induced adipose dysfunction.

Herbal Combination of Phyllostachys pubescens and Scutellaria baicalensis Inhibits Adipogenesis and Promotes Browning via AMPK Activation in 3T3-L1 Adipocytes

“…To further elucidate the mechanism underlying the anti-obesity effects of BS21, we measured marker proteins of BAT (PR domain containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1α), and UCP1) involved in adaptive thermogenesis and the transition of WAT to brown-like adipose tissue [ 25 ]. In addition, the activated β-adrenergic signaling cascade (protein kinase A, AMPK, p38, and extracellular signal-regulated kinase) induces white fat browning and brown fat development by elevating PGC1α, PRDM16, PPARγ, and UCP1 [ 26 , 27 , 28 , 29 ]. In this study, BS21 treatment induced AMPK activation and the expression of brown adipocyte marker proteins in 3T3-L1 adipocytes.…”

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…These animals also showed an improvement in the inflammatory profile in scWAT and BAT. Finally, a Grape pomace extract (GPE) showed the capacity to induce browning (upregulation of Pgc1α, Pparγ, Prdm16 and Ucp1 ) in the eWAT of HFD-fed rats [ 179 , 180 ].…”

Uncovering the Role of p38 Family Members in Adipose Tissue Physiology

“…The SNS induces the release of cathecolamines like norepinephrine, which, through binding to β 3AR, trigger PKA and p38 activation and promote UCP1 transcription partly via p38-mediated modulation of ATF2 and PGC1 α transcriptional activity ( 129 ) ( Figure 4 ). UCP1 expression is also activated via β 3AR-stimulated p38 activation by a series of naturally occurring compounds, such as thymol ( 130 ), cinnamaldehyde ( 131 ), L-rhamnose ( 132 ), grape pomace extract ( 133 ), and mangiferin ( 134 ). Along with β 3AR pathway induction, cold-induced WAT browning is also mediated by stimulation of the histamine H4 receptor, which acts through intracellular calcium mobilization and p38 and ERK activation, promoting PGC1 α and UCP1 expression ( 135 ).…”