Germacrone inhibits adipogenesis and stimulates lipolysis via the AMP-activated protein kinase signalling pathway in 3T3-L1 preadipocytes.

Objectives: In a previous study, we reported that Aster spathulifolius Maxim extract (ASE) inhibited lipid accumulation and adipocyte differentiation in 3T3-L1 cells. Of the components in ASE, germacrone (GM) was identified as a potent bioactive constituent. GM is known for its anticancer and antiviral activity. However, the effects of GM and the molecular mechanism by which GM regulates adipogenesis and lipolysis were not reported. Therefore, we investigated the effect of GM on adipogenesis and lipolysis and to elucidate its underlying molecular mechanism.

Methods: We analysed the contents of intracellular triglyceride and carried out Western blotting and RT-qPCR to investigate the underlying mechanism.

Key Findings: We demonstrate that GM suppresses adipogenic differentiation and the increase in lipolysis in 3T3-L1 cells. In particular, GM down-regulates the expression of early adipogenesis-related genes (e.g. KLF4, KLF5, C/EBP-β and C/EBP-δ) and major adipogenesis-related genes (C/EBP-α and PPAR-γ). Furthermore, GM increases the protein levels of phosphorylated AMP-activated protein kinase α (AMPKα), phosphorylated acetyl-coenzyme A carboxylase (ACC) and carnitine palmitoyltransferase (CPT1).

Conclusions: Our results suggest that GM may be a potent bioactive anti-adipogenic and lipolytic constituent via the regulation of adipogenesis, lipolysis and the AMPKα pathway.