Caffeic Acid Phenethyl Ester Improves Metabolic Syndrome by Activating PPAR‐γ and Inducing Adipose Tissue Remodeling in Diet‐Induced Obese Mice

Scope This study investigated the effects of caffeic acid phenethyl ester (CAPE), a bioactive component of honeybee hives, on the prevention and treatment of metabolic syndrome (MetS) by comparing the efficacy of CAPE intake at the beginning of obesity and after obesity. The functional mechanism of CAPE was also investigated. Methods and results C57BL/6 mice were fed a high‐fat diet (HFD) containing 0.05% CAPE (HFD+C) for 12 weeks (HFD+C(Pre) group) or received HFD+C for 6 weeks after consuming the HFD for 6 weeks (HFD+C(Post) group). Both CAPE‐fed groups showed significant improvements in body weight, fatty liver, inflammation, and insulin resistance, but not serum lipid levels. Hyperlipidemia was only ameliorated in the HFD+C(Pre). Adipose tissue (AT) remodeling occurred in the CAPE‐fed groups. Specifically, CAPE induced PPAR‐γ activation, resulting in adipogenesis, a smaller and more uniform distribution of adipocytes, and decreased immune cell penetration and inflammation; CAPE also improved the disturbed pattern of adipokine secretion. Hypoxia was improved by promoting angiogenesis in AT. Conclusion CAPE ameliorates metabolic disease by inducing PPAR‐γ activation and AT remodeling. Additionally, this study reveals that the intake of CAPE after obesity, as well as in the early stage of obesity, helps in the prevention and treatment of MetS. Caffeic acid phenethyl ester (CAPE) promotes PPAR‐γ activity, resulting in adipogenesis, a smaller and more uniform distribution of adipocytes, and decreased immune cell penetration and inflammation; CAPE also improves the disturbed secretion pattern of adipokines. Through the PPAR‐γ activation and adipose tissue (AT) remodeling, CAPE stably stores excess energy in AT, improving metabolic diseases such as hyperlipidemia, fatty liver, inflammation, and insulin resistance.