Equisetin inhibits adiposity through AMPK-dependent regulation of brown adipocyte differentiation

Obesity has a significant impact on endocrine function, which leads to metabolic diseases including diabetes, Insulin resistance, and other complications associated with obesity. Development of effective and safe anti-obesity drugs is imperative and necessary. Equisetin (EQST), a tetramate-containing marine Fungal product, was reported to inhibit Bacterial fatty acid synthesis and affect Mitochondrial Metabolism. It is tempting to speculate that EQST might have anti-obesity effects. This study was designed to explore anti-obesity effects and underlying mechanism of EQST on 3T3-L1 adipocytes differentiated from 3T3-L1 cells. Oil Red O staining showed that EQST reduced lipid accumulation in 3T3-L1 adipocytes. Quantitative real-time polymerase chain reaction and Western blot analysis revealed that EQST significantly inhibited expression of adipogenesis/lipogenesis-related genes C/ebp-α, Ppar-γ, Srebp1c, Fas, and reduced protein levels. There was also increased expression of key genes and protein levels involved in lipolysis (Perilipin, ATGL, Hsl), brown adipocyte differentiation (Prdm16, Ucp1), mitochondrial biogenesis (Pgc1α, Tfam) and β-oxidation Acsl1, Cpt1. Moreover, mitochondrial content, their membrane potential ΔΨM, and respiratory chain genes Mt-Co1, Cox7a1, Cox8b, and Cox4 (and protein) exhibited marked increase in expression upon EQST treatment, along with increased protein levels. Importantly, EQST induced expression and activation of AMPK, which was compromised by the AMPK Inhibitor dorsomorphin, leading to rescue of EQST-downregulated Fas expression and a reduction of the EQST-increased expression of Pgc1α, Ucp1, and Cox4. Together, EQST robustly promotes fat clearance through the AMPK pathway, these results supporting EQST as a strong candidate for the development into an anti-obesity therapeutic agent.

AMPK pathway; Adipogenesis; Brown adipocyte; Equisetin (EQST); Lipogenesis; Mitochondrial biogenesis.