Falcarindiol promotes beige adipocyte-related gene expression and mitochondrial respiration in human preadipocyte-derived adipocytes

Falcarindiol, a typical polyacetylene compound found in Apiaceae vegetables, activates peroxisome proliferator-activated receptor γ (PPARγ). However, whether it induces the browning of adipocytes through PPARγ activation is unclear. In this study, we aimed to clarify the effects of falcarindiol on adipocyte browning and mitochondrial respiration in human preadipocyte-derived adipocytes. Human primary cultured cells were differentiated for 8 days in the presence of falcarindiol. The expression of PPARγ target and beige adipocyte-related genes was measured using quantitative real-time PCR, and the accumulation of lipid droplets and uncoupling protein 1 (UCP1) protein expression were evaluated using immunohistochemistry. The oxygen consumption rate was measured using a Seahorse flux analyzer. Falcarindiol increased the expression of PPARγ target genes, including <i>PPARγ</i>, <i>FABP4</i>, <i>SLC2A4</i>, and <i>ADIPOQ</i>. It also increased the expression of beige adipocyte-related genes, such as <i>PPARGC1A</i>, <i>PPARA</i>, <i>CITED1</i>, and <i>TBX1</i>, and increased the expression of UCP1 protein. Falcarindiol also significantly increased basal respiration, ATP-linked respiration, maximal respiration, spare capacity, and proton-leak respiration, and significantly decreased the coupling efficiency in a concentration-dependent manner. These results indicate that falcarindiol promotes a beige adipocyte-like phenotype and oxygen consumption of adipocytes in vitro, suggesting that dietary intake of falcarindiol and falcarindiol-containing Apiaceae vegetables may be effective in obesity prevention.