Quercetin mitigates high-fat diet-induced glucose intolerance in part inducing FNDC5/irisin in muscle and in L6 myotubes and white adipose tissue browning.

PERDICARO DJ; RODRIGUEZ LANZI C; MUSCIA V; OTEIZA PI; VAZQUEZ PRIETO MA

Buenos Aires

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

SAIC SAFIS SAI

Irisin is an exercise-induced myokine that can induce browning of white adipose tissue (WAT) and other metabolic benefits. We previously observed that supplementation with the flavonoid quercetin (Q) mitigated high-fat diet (HFD)-induced glucose intolerance and adipose hypertrophy. In this study, we investigated whether these beneficial effects could be related to Q capacity to activate muscle FNDC5/irisin and uncoupling protein-1 (UCP-1) and others brown markers in the WAT of HFD fed rats. Also, the role of Q on FNDC5/irisin was further investigated in vitro in L6 myotubes triggered with palmitate. Co-administration of Q (20 mg/kg body weight/d) to the HFD during 8 weeks significantly increased FNDC5/irisin pathway and p-AMPK and p-p38 in skeletal muscle compared to the control and HFD groups. In addition, Q significantly upregulated proteins involved in WAT browning (PRDM16, PGC1-α, PPARɣ and UCP-1) compared with control and HFD groups. Moreover, in the HFD+Q group we observed a partial and significant BAT weight increase compared to the HFD and Ctrl groups, respectively. In L6 myotubes Q prevented palmitate-decrease GLUT4, PGC1-α and irisin secretion. Q 1 µM also prevented palmitate-downregulated mRNA levels of Pgc1a and Fndc5. In addition, PGC-1α siRNA transfection in L6 myotubes abrogated the effects of Q on FNDC5 protein expression. These data suggest that Q activated FNDC5/irisin pathway, in part via PGC-1α activation. Overall, Q supplementation enhanced FNDC5/irisin pathway in L6 myotubes and muscle, activated AMPK, p38 MAPK and GLUT4 in muscle and induced adipose tissue browning in the WAT of rats fed a HFD. These findings support the potential relevance of consuming Q-rich foods or supplements to attenuate high fat diet-induced metabolic alterations.