Quercetin mitigate high-fat-induced glucose intolerance and adipose hypertrophy in part inducing FNDC5/irisin in muscle

PERDICARO, DIAHANN J.; MUSCIA, VICTORIA; RODRIGUEZ LANZI, CECILIA; OTEIZA, PATRICIA I.; VAZQUEZ PRIETO, MARCELA A.

Friburgo de Brisgovia

Congreso; V International Congress in Translational Medicine; 2021

Irisin is an exercise-induced myokine that can induce browning of white adipose tissue (WAT) as well as other metabolic benefits. We previously observed that supplementation with the flavonoid quercetin (Q) mitigated high-fat diet (HFD)-induced visceral adipose hypertrophy, inflammation and insulin resistance. In this study, we investigated whether these beneficial effects could be also related to Q capacity to activate muscle FNDC5/irisin and uncoupling protein-1 (UCP-1) as well as others brown fat markers in the WAT. The role of Q on FNDC5/irisin was further investigated in vitro in L6 myotubes triggered with palmitate. Consumption of a HFD for 6 weeks reduced the protein levels of PGC1-α in skeletal muscle compared to the control group, while no differences were observed in the protein levels of FNDC5, p-AMPK, p-p38 and GLUT4 among control and HFD groups. However, the co-administration of Q to the HFD significantly increased p-AMPK, p-p38 and the FNDC5/irisin pathway. In addition, Q upregulated the levels of proteins involved in the browning of WAT (PRDM16, PGC1-α, PPARɣ and UCP-1) compared with control and HFD groups. In L6 myotubes Q prevented palmitate-decrease GLUT4 and PGC1-α protein levels and significantly increased irisin protein expression and secretion. Q 1 µM also prevent palmitate-downregulated mRNA levels of Pgc1-α and Fndc5. When L6 myotubes where transfected with Pgc-1α siRNA we observed that Pgc-1α was involved in the Q-mediated upregulation of FNDC5. Overall, Q supplementation could contribute to attenuate HFD-induced adipose hypertrophy and related pathologies, i.e. insulin resistance in part due to an increase in FNDC5/irisin pathway and p-AMPK in muscle, and by promoting WAT browning.