Grape pomace extract supplementation activates FNDC5/irisin in muscle and promotes white adipose browning in rats fed a high-fat diet.

PERDICARO DJ; FONTANA A; RODRIGUEZ LANZI C; MUSCIA V; VAZQUEZ PRIETO MA; GAMBARTE TUDELA J; OTEIZA P; PERDICARO DJ; FONTANA A; RODRIGUEZ LANZI C; MUSCIA V; VAZQUEZ PRIETO MA; GAMBARTE TUDELA J; OTEIZA P

Congreso; Sociedad Argentina de Fisiologia; 2019

Increased visceral adiposity plays an important role in the physiopathology of obesity and is related to altered glucose tolerance. Thus, promoting strategies to prevent these complications might be relevant. Concerning to this, phenolic compounds (PC) are molecules widely distributed in fruits and vegetables with proved beneficial effects. In addition, grape pomace extract (GPE) is a concentrate product obtained from a winemaking- residue with a relative high concentration of PC, (-)-epicatechin (EC) is one of the most relevant. On the other hand, Irisin is a novel myokine activates by PGC-1α in exercising muscles, that is released into the bloodstream after cleavage of fibronectin type 3 domain containing protein 5 (FNDC5). Irisin is related with adipose tissue?browning? and increased glucose tolerance. Recent evidence suggest that PC are able to activate Irisin. The aim of this study was to evaluated the effects of GPE supplementation: i. in the activation, secretion and possible underling mechanism of FNDC5/Irisin pathway on muscles of HFD-rats and L6 myotubes and ii. on epididymal adipose tissue (eWAT) ?browning?, adiposity and glucose tolerance on HFD-rats. Results: GPE activates the FNDC5/Irisin pathway and enhances Irisin secretion in vivo and in vitro, at least in part via PGC-1α activation.GPE prevents HFD-induced adipocyte hypertrophy and insulin resistance. In adittion, GPE activates eWAT ?browning? evidence by increased protein levels of PGC-1α, PPARγ, PRDM16 and UCP-1. Finally, GPE induced AMPK-phosphorylation on muscles. Conclusions: Together, our findings demonstrate that GPE activates the FNDC5/Irisin pathway, which is associated with eWAT ?browning?. This can in part underlie the GPE capacity to prevent HFD-induced adiposity and insulin resistance.