Black tea is a kind of full-fermented tea with therapeutic potential for metabolic diseases. Ectopic lipid deposition (ELD) is an essential risk factor for organ injury in metabolic syndrome, especially in liver and kidney, for which effective interventions are lacking. Here, we explored whether black tea extract (BTE) improves fatty liver and fatty kidney, as well as identified the potential lipid biomarkers for ELD and lipid targets of BTE on the improvement of ELD. Transcriptome data from diet-induced obese (DIO) mice were analyzed to confirm high-fat-diet feeding disturbs lipid metabolism in the liver and kidney. BTE prominently inhibited body weight gain, improved glucose metabolism, as well as reduced lipid droplet accumulation in the liver and kidney. Moreover, lipidomic profiling analyses identified 28 lipid classes in the liver while 29 in the kidney with that up-regulated glycerides and phosphatidylcholines (PC), as well as down-regulated cardiolipin (CL) were the characteristic changes in ELD. BTE prominently reduced glycerides in ELD, thereby constituting the basis of its anti-ELD effect. Specifically, BTE displayed stronger effects on lowering cholesterol ester (CE) in fatty liver, while also affecting phospholipids and sphingolipids in fatty kidney. Ultimately, integrative analysis identified CE18:2 and triglyceride (TAG) 56:4 (20:2) as the potential lipid biomarkers for BTE in improvement of ELD. BTE could be an effective food supplement for the prevention and treatment of ELD. Notably, CE18:2 and TAG56:4 (20:2), as the potential lipid biomarkers, may facilitate the research and development of anti-ELD drug.

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 diet-induced obesity 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 protein kinase B (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 BTE 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.

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.