Sodium Houttuybonate Promotes the Browning of White Adipose Tissue by Inhibiting Ferroptosis via the AMPK-NRF2-HO1 Pathway

Abstract

The rising prevalence of obesity has resulted in an increased demand for innovative and effective treatment strategies. Houttuynia cordata Thunb. (H. cordata) has demonstrated promising potential in preventing obesity. However, the mechanism underlying the anti-obesity effects of H. cordata and its bioactive component, sodium houttuybonate (SH), remains unclear. Our study reveals that SH treatment promotes the browning of inguinal white adipose tissue (iWAT) and prevents the obesity induced by a high-fat diet. SH significantly mitigates ferroptosis by upregulating glutathione peroxidase 4 (Gpx4) and decreasing malondialdehyde (MDA) levels, while also enhancing superoxide dismutase (SOD) levels. Furthermore, SH promotes the phosphorylation of AMP-activated protein kinase (AMPK), which subsequently increases the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) in the iWAT. However, the effects of SH were attenuated by ML385, an Nrf2 inhibitor. Collectively, our findings suggest that SH induces iWAT browning and prevents diet-induced obesity primarily through the AMPK/NRF2/HO-1 pathway by inhibiting ferroptosis.