LAUSR

Abstract The objective was to examine the effectiveness of mate tea (MT, Ilex paraguariensis St. Hilaire) and caffeine from mate tea (MC) on in vitro lipid accumulation and in vivo diet-driven-obesity. MC and decaffeinated mate (DM) were obtained using supercritical CO2 extraction and mainly composed of caffeine and caffeoylquinic acids, respectively. MC reduced lipid accumulation (41%) via downregulation of fatty acid synthase (Fasn) (39%) in 3T3-L1 adipocytes. Rats fed a high-fat-high-sucrose-diet and 0.1% of caffeine from MC, MT, or DM. MC attenuated weight gain (16%) and body fat accumulation (22%). MC reduced Fasn expression in both adipose tissue (66%) and liver (37%). MC diminished pyruvate kinase (PK, 59%) and microsomal triglyceride transfer protein (MTP, 50%) hepatic expression. In silico, neochlorogenic acid interacted with PK and MTP allosteric sites. FAS β‐ketoacyl reductase domain showed the highest affinity to 3,5-dicaffeoylquinic acid. Caffeine suppressed lipid accumulation and body weight gain, through the modulation of lipogenic gene expression.