Abstract
Erianin, a natural bibenzyl compound, has recently garnered attention owing to its diverse biological activities. In the present study, we investigated the effects of Erianin on adipocyte differentiation, lipid metabolism, and mitochondrial respiration in murine 3T3-L1 cells. Cytotoxicity assays indicated that Erianin exhibited low toxicity towards preadipocytes at concentrations up to 200 μM. Treatment with 20 μM Erianin completely inhibited the differentiation of 3T3-L1 preadipocytes into mature adipocytes and reduced lipid droplets. Western blot analysis revealed that Erianin attenuated Akt and p38 MAPK signalling without inducing apoptosis, suppressed the expression of key pro-adipogenic transcription factors, C/EBPα and PPARγ during the early stages of differentiation. This suppression was accompanied by the downregulation of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), pyruvate carboxylase (PC) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). While early-stage differentiation was robustly inhibited, higher concentrations (≥25 μM) were required to suppress terminal differentiation of immature adipocytes. This late-stage inhibition was accompanied by decreased expression of PPARγ, PC, and HMGCR, with minimal effects on ACC1 and FASN, suggesting a more modest role for Erianin in terminal adipogenesis. Assessment of mitochondrial metabolism of 3T3-L1 cells following 24-hour treatment of Erianin showed that it modestly impaired ATP-linked respiration, maximal respiration, spare respiratory capacity and intracellular ATP levels while basal respiration was unaffected. Collectively, these findings indicated that Erianin predominantly targets early adipogenic differentiation and mitochondrial bioenergetics.