PMID- 31998896 OWN - NLM STAT- MEDLINE DCOM- 20201123 LR - 20201123 IS - 2042-650X (Electronic) IS - 2042-6496 (Linking) VI - 11 IP - 2 DP - 2020 Feb 26 TI - Grape pomace extract supplementation activates FNDC5/irisin in muscle and promotes white adipose browning in rats fed a high-fat diet. PG - 1537-1546 LID - 10.1039/c9fo02463h [doi] AB - Irisin is a myokine regulated by peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) in the exercising skeletal muscle and released into the bloodstream after cleavage of FNDC5. Circulating irisin can up-regulate UCP-1 expression in white adipose tissue (WAT) promoting the formation of brown-like adipocytes. The aim of this study was to evaluate if supplementation with a grape pomace extract (GPE) could activate the FNDC5/irisin pathway via PGC-1alpha in rats fed a high fat diet (HFD). For this purpose we characterized the activation of: i. the FNDC5/irisin pathway and AMPK in skeletal muscle and ii. proteins involved in the formation of brown-like cells in epididymal WAT (eWAT). Consumption of the GPE activated the FNDC5/irisin pathway, increased AMPK phosphorylation in skeletal muscle and enhanced irisin plasma levels. In eWAT, the GPE increased the level of proteins involved in WAT browning, i.e. PGC-1alpha, PPARgamma, PRDM16 and UCP-1. The GPE also prevented HFD-induced adipocyte hypertrophy and systemic insulin resistance. Consistently, in L6 myotubes, (-)-epicatechin (EC), a flavonoid abundant in the GPE, prevented palmitate-mediated downregulation of FNDC5/irisin protein expression and secretion, in part via PGC-1alpha activation. Consumption of the GPE, a winemaking residue rich in bioactive compounds, could be a beneficial strategy to counteract the adverse effects of Western style diets through the promotion of WAT browning. FAU - Rodriguez Lanzi, Cecilia AU - Rodriguez Lanzi C AD - Laboratorio de Nutricion y Fisiopatologia de la Obesidad, Instituto de Medicina y Biologia Experimental de Cuyo (IMBECU)-CONICET, Mendoza, Argentina. mvazquez@fcm.uncu.edu.ar. FAU - Perdicaro, Diahann J AU - Perdicaro DJ FAU - Gambarte Tudela, Julian AU - Gambarte Tudela J FAU - Muscia, Victoria AU - Muscia V FAU - Fontana, Ariel R AU - Fontana AR FAU - Oteiza, Patricia I AU - Oteiza PI FAU - Vazquez Prieto, Marcela A AU - Vazquez Prieto MA LA - eng PT - Journal Article PL - England TA - Food Funct JT - Food & function JID - 101549033 RN - 0 (FNDC5 protein, rat) RN - 0 (Fibronectins) RN - 0 (Plant Extracts) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/drug effects/metabolism MH - Adipose Tissue, Brown/drug effects/metabolism MH - Adipose Tissue, White/*drug effects/metabolism MH - Animals MH - Diet, High-Fat MH - Fibronectins/*metabolism MH - Male MH - Mice MH - Muscle, Skeletal/*drug effects/metabolism MH - Plant Extracts/*pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - *Vitis EDAT- 2020/01/31 06:00 MHDA- 2020/11/24 06:00 CRDT- 2020/01/31 06:00 PHST- 2020/01/31 06:00 [pubmed] PHST- 2020/11/24 06:00 [medline] PHST- 2020/01/31 06:00 [entrez] AID - 10.1039/c9fo02463h [doi] PST - ppublish SO - Food Funct. 2020 Feb 26;11(2):1537-1546. doi: 10.1039/c9fo02463h.