Mitophagy suppression by miquelianin‐rich lotus leaf extract induces ‘beiging’ of white fat via AMPK/DRP1‐PINK1/PARKIN signaling axis

Abstract

AbstractBackgroundLotus (Nelumbo nucifera) leaf has been described to have anti‐obesity activity, but the role of white fat ‘browning’ or ‘beiging’ in its beneficial metabolic actions remains unclear. Here, 3T3‐L1 cells and high‐fat‐diet (HFD)‐fed mice were used to evaluate the effects of miquelianin‐rich lotus leaf extract (LLE) on white‐to‐beige fat conversion and its regulatory mechanisms.ResultsTreatment with LLE increased mitochondrial abundance, mitochondrial membrane potential and NAD+/NADH ratio in 3T3‐L1 cells, suggesting its potential in promoting mitochondrial activity. qPCR and/or western blotting analysis confirmed that LLE induced the expression of beige fat‐enriched gene signatures (e.g. Sirt1, Cidea, Dio2, Prdm16, Ucp1, Cd40, Cd137, Cited1) and mitochondrial biogenesis‐related markers (e.g. Nrf1, Cox2, Cox7a, Tfam) in 3T3‐L1 cells and inguinal white adipose tissue of HFD‐fed mice. Furthermore, we found that LLE treatment inhibited mitochondrial fission protein DRP1 and blocked mitophagy markers such as PINK1, PARKIN, BECLIN1 and LC‐3B. Chemical inhibition experiments revealed that AMPK/DRP1 signaling was required for LLE‐induced beige fat formation via suppressing PINK1/PARKIN/mitophagy.ConclusionOur data reveal a novel mechanism underlying the anti‐obesity effect of LLE, namely the induction of white fat beiging via AMPK/DRP1/mitophagy signaling. © 2023 Society of Chemical Industry.