Miquelianin, a main functional flavonoid of lotus leaf, induces thermogenic signature via p38‐PINK1‐PARKIN‐mediated mitophagy and mimicking NRF2 signaling during brown adipocyte differentiation

Adipocytes thermogenesis is an important mechanism for increasing energy expenditure. Here, screening of thermogenic activators (Sirt1 and Ucp1) investigated in C3H10T1/2 cells revealed ethanol extract lotus leaf (LLE) may exert higher activity compared with that the other 11 ingredients. UPLC-MS/MS analysis showed miquelianin was identified as main flavonoid compounds LLE (12.8%) therefore deserves further investigation. The results promoted lipolysis, enhanced programming (Sirt1, Ppargc1a, Prdm16, Cox7a, Nrf1, Cox2, Ucp1), induced brown-like adipocyte formation (Fgf21, Cd137, Tmem26, Tbx1, Cd40, Cited1). Moreover, increased mitochondrial abundance, membrane potential, NAD+/NADH ratio, suggesting its potential mitochondria activity. We also observed improved quality by establishment dynamics (Mfn1, Mfn2, Opa1, Drp1, Fis1) subsequent suppression autophagy. Chemical inhibition experiment trigger browning via p38-PINK1-PARKIN-mediated mitophagy. Furthermore, ML385-treated cells, NRF2, HMOX1, TFAM, UCP1 were compromised treatment, NRF2 signaling necessary during miquelianin-induced biogenesis. Together, our findings demonstrate induce programing suppressing mitophagy p38-PINK1-PARKIN mimicking signaling.