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

• Published in: Food & function Vol. 11; no. 2; pp. 1537 - 1546
• Main Authors: Rodriguez Lanzi, Cecilia, Perdicaro, Diahann J, Gambarte Tudela, Julián, Muscia, Victoria, Fontana, Ariel R, Oteiza, Patricia I, Vazquez Prieto, Marcela A
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 26.02.2020
• Subjects: Activation; Adipocytes; Adipose tissue; Bioactive compounds; Browning; Consumption; Diet; Dietary supplements; Epicatechin; Flavonoids; Grapes; High fat diet; Hypertrophy; Insulin; Muscles; Musculoskeletal system; Myotubes; Palmitic acid; Phosphorylation; Plasma levels; Proteins; Skeletal muscle
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c9fo02463h

Irisin is a myokine regulated by peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) 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-1α 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-1α, PPARγ, 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-1α 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.