Grape pomace extract, rich in polyphenols, stimulate the emergence of brown-like cells in white adipose tissue in spontaneously hypertensive rats and in 3T3-L1 adipocytes

This study investigated the effect of grape pomace extract (GPE) on brown-like induction in epididymal white adipose tissue (eWAT) from spontaneously hypertensive rat (SHR) receiving a high-fat diet (HF) and in 3T3-L1 adipocytes. HF increased eWAT adiposity and diameter in Wistar Kyoto (WKY) but not in SHR, while GPE (300 mg/kg/day) supplementation reduced adipocyte diameter in WKY and attenuated adipose inflammation in both strain. In contrast, GPE increase protein levels involved in the “browning” such as PGC-1a, PPARγ and UCP-1 from SHR eWAT. In differentiated adipocytes from SHR eWAT, UCP-1 protein levels significantly decreased in cells pre-treated with SB203580 (p38 inhibitor) or U0126 (ERK inhibitor) but not in cells treated with GPE alone suggesting that GPE enhance UCP-1 in part via p38 and ERK. In 3T3-L1 adipocytes treated with palmitate the pretreatment with GPE (30 mM) enhances the activation of the downstream of β-adrenergic signaling cascade (PKA, AMPK, p38, ERK) in part involved in mitochondrial biogenesis (UCP-1, PPARγ and PGC-1α) and in fatty acid oxidation (ATGL). These effects were comparable when epicatechin or quercetin (1 µM), the main flavonoids found in GPE, was used. Overall, GPE could induce brown-like adipocytes in white adipocytes supporting the utilization of winemaking residues, rich in polyphenols, to treat obesity or related diseases.