Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α Pathway

Pharmacological activation of adaptive thermogenesis to increase energy expenditure is considered to be a novel strategy for obesity. Peroxisome-proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), which serves as an inducible co-activator in energy expenditure, is highly expressed in brown adipose tissues (BAT). In this study, we found a PGC-1 alpha transcriptional activator, natural compound rutaecarpine (Rut), which promoted brown adipocytes mitochondrial biogenesis and thermogenesis in vitro. Chronic Rut treatment reduced the body weight gain and mitigated insulin sensitivity through brown and beige adipocyte thermogenesis. Mechanistic study showed that Rut activated the energy metabolic pathway AMP-activated protein kinase (AMPK)/PGC-1 alpha axis, and deficiency of AMPK abolished the beneficial metabolic phenotype of the Rut treatment in vitro and in vivo. In summary, a PGC-1 alpha transcriptional activator Rut was found to activate brown and beige adipose thermogenesis to resist diet-induced obesity through AMPK pathway. Our findings serve as a further understanding of the natural compound in adipose tissue and provides a possible strategy to combat obesity and related metabolic disorders.