In this study, we investigated the effects of dark tea with Pericarpium Citri Reticulatae on body mass growth (BMG), fasting serum glucose (FSG), glucose tolerance (GT), serum insulin, serum lipids and gut microbiota in C57BL/6J mice with metabolic disorders induced by a high-fat diet. Our data showed that intervention with the tea at a dose of 0.75–3.00 g/kg m_b lowered FSG in the mouse model of metabolic disorders. The intervention at 3.00 g/kg m_b improved GT and ameliorated early hepatic fat deposition. Hepatic total cholesterol was decreased significantly in the middle-dose (1.50 g/kg m_b) intervention group. Moreover, consumption of the dark tea reversed the change in gut microbiota relative abundance induced by the high-fat diet and decreased the relative abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes. At the genus level, the dark tea inhibited the relative abundance of Desulfovibrio, Lactobacillus and Lactococcus but increased the abundance of Clostridium and Lachnospiraceae_NK4A136_group. Metabolic pathway analysis revealed that lactate dehydrogenase and 6-phospho-β-glucosidase, key enzymes of glycolysis, were down-regulated, resulting in inhibition of the synthesis of lipoteichoic acid associated with the enrichment and adhesion of Gram-positive bacteria. Based on these findings, we speculated that dark tea with Pericarpium Citri Reticulatae may protect the intestinal epithelial barrier and regulate fatty acid absorption, bile acid metabolism and lipolysis, thereby ameliorating glucose metabolism and liver fat deposition. Thus, this tea is expected to be a potential healthy beverage regulating the gut microbiota and improving glucose and lipid metabolism.

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.