Abstract
A rise in obesity during the COVID-19 pandemic has spurred the development of safe and effective natural anti-obesity agents. In this study, we propose Rubia akane Nakai fruit extract (RFE) as a potential natural product-based anti-obesity agent. R. akane Nakai is a plant of the Rubiaceae family that grows throughout Republic of Korea. Its roots have long been used medicinally and are known for various bioactivities, but the fruit's bioactivities are unexplored. We investigated the anti-obesity effects of RFE using 3T3-L1 adipocytes and high-fat diet-induced obese mice. In 3T3-L1 adipocytes, RFE inhibited adipogenic differentiation and lipogenesis by downregulating PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT enhancer-binding protein α), and SREBP-1 (sterol regulatory element-binding protein 1) through AMPK (AMP-activated protein kinase) activation and by delaying the initiation of MCE (mitotic clonal expansion), which is essential for early adipogenesis. At the in vivo level, RFE improved the phenotypes of obesity and insulin resistance. In white adipose tissue, RFE not only suppressed adipogenic differentiation and lipogenesis through AMPK activation but also improved insulin sensitivity by upregulating basal GLUT4 (glucose transporter type 4) expression. Therefore, this study advances RFE as a potential natural treatment for obesity and insulin resistance.