Scope
Piperonal is an aromatic compound found in vanilla and has a floral odor resembling vanillin. This study was aimed to test whether piperonal attenuates visceral adiposity induced by a high‐fat diet (HFD) in mice and to explore the underlying molecular mechanisms.
Methods and results
Male C57BL/6N mice were fed a normal diet, HFD, or 0.05% piperonal‐supplemented HFD (PSD) for 10 weeks. PSD‐fed mice showed attenuation of body weight gain, total visceral fat pad weights, and plasma lipid levels compared to HFD‐fed mice. Piperonal supplementation of the HFD increased the mRNA expression of certain isotypes of adenylate cyclase (Adcy) and protein kinase A (PKA) in the white adipose tissue (WAT) of mice. The adipogenesis‐related genes were downregulated, whereas fatty acid oxidation‐ and thermogenesis‐related genes were upregulated in the WAT of PSD‐fed mice compared to those in HFD‐fed mice. Piperonal directly activated Adcy by decreasing the Km for its substrate (ATP) in plasma membranes prepared from the WAT of mice. Furthermore, piperonal‐induced inhibition of adipocyte differentiation and elevation of Adcy and PKA activities in 3T3‐L1 cells were abrogated by an Adcy inhibitor.
Conclusion
The anti‐adipogenic effect of piperonal in mice fed the high‐fat diet appears to be associated with increased Adcy–PKA signaling in WAT.