The emergence of meal replacement (MR) originates from physical exercise or fitness as a substitute for one or all meals and later expands to the field of weight loss. Indeed, the main application of current meal replacement is to lose body weight, whether patients with obesity, diabetes, fatty liver, infertile or pregnant women can benefit from weight loss. In addition, MRs still exhibit more biomedical potential in preventing and treating diseases, like anti-diabetes, improving fatty liver and kidney disease, preventing cancer, conceiving and reducing pregnancy complications, and improving life quality. Indeed, there are also disadvantages to meal replacement, including causing adverse effects, although most are acceptable and tolerated. To date, various commercially-developed MRs are walking from dining table to sickbed. Therefore, a scientific understanding of the advantages and disadvantages of meal replacements is crucial for their extensive application beyond biomedical potentials.

Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a “disease”. Brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning emerge as a potential strategy of anti-obesity by dissipating energy as heat. However, drugs based on adipose tissue thermogenesis have not been successfully approved yet. In current study, we found that black tea extract (BTE) obtained by patent-authorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity, improvement of adipose distribution, and glucose metabolism improvement in DIO mice. Mechanismly, anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1 (UCP1), especially visceral adipose tissue (VAT) with browning resistance. Specifically, utilizing in silico approach of network pharmacology and molecular docking, we identified carbonic anhydrase 2 (CA2) in nitrogen metabolism as anti-obesity target of BTE and further elucidated that AKT signaling pathway linked CA2 and UCP1. Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation. Our findings demonstrated anti-obesity effect of black tea extract as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway, which could be developed as promising anti-obesity agent with good safety and efficacy.