Grape pomace extract, rich in polyphenols, induced the emergence of brown-like cells in white adipose tissue from spontaneously hypertensive rats receiving a high-fat diet and in adipocytes.

ANDREA ANTONIOLLI; PERDICARO DAHIANNE; CECILIA RODRIGUEZ LANZI; ARIEL RAMON FONTANA

Mendoza

Congreso; Congreso Argentino de Hipertensión Arterial. Sociedad Argentina de Hipertensión; 2017

SAHA

Recruitment of brown-like cells in white adipose tissue has become an interesting therapeutic approach to treat obesity, due to brown adipocytes have a high content of mitochondria expressing the uncoupling protein 1 (UCP1). In this study, we determinate the capacity of malbec grape pomace extract (GPE) to modulate proteins involved in mitochondrial biogenesis in epididymal visceral adipose tissue (eVAT) from spontaneously hypertensive rats (SHR) receiving a high-fat diet (HFD) and in a primary cultures of rat adipocytes and in 3T3-L1 pre-adipocytes. Ten weeks old SHR and WKY (Wistar-Kyoto) rats were divided into three groups: Control group (n=4); WKY/ SHR-HFD group receiving fat (40% (w/w), n=6); and WKY/SHR HFD supplemented with GPE (300 mg/Kg/d, n=6) for 10 weeks. HFD leads to an increased epididymal adipose weight and diameter accompanied with high levels of free fatty acid (FFA) in WKY rats, while no significantly changes were observed in adipose weight and size in SHR. GPE supplementation decreased the adipocyte size and plasma levels of FFA and triglycerides in WKY without changes in adipose weight, while in SHR GPE increased HDL cholesterol and decrease the systolic blood pressure. Interestingly, GPE supplementation enhances UCP-1 expression and proteins involved in mitochondrial biogenesis such as PGC-1α and PPARɣ in SHR but not in WKY rats. In order to explore the underlying mechanisms cells from stromal vascular fraction from eWAT were isolated and differentiated to adipocytes. UCP-1 expression was significantly decreased in adipocytes from SHR when cells were pre-treated with a p38 and ERK inhibitor suggesting that GPE enhance UCP-1, in part via p38 and ERK. In 3T3-L1 adipocytes stimulated with palmitate GPE (30 µM) enhances the downstream of β-adrenergic signaling cascade (PKA, AMPK, p38, ERK, ATGL) in part involved in mitochondrial biogenesis. GPE can stimulate the emergence of brown-like cells and may protect against diet-induced adipose dysfunction.