Differential Regulation of Hepatic Cholesterol Metabolism by Water Extract or Residue of Large‐Leaf Yellow Tea in High‐Fat Diet‐Fed Mice

ABSTRACT As a slightly fermented tea in China, large‐leaf yellow tea (YT) has demonstrated a capacity to ameliorate lipid metabolism disorders (LMDs) induced by a high‐fat diet (HFD). Tea residue, as a byproduct of tea infusion, is increasingly recognized for its potential in reuse and high‐value utilization. The objective of our research was to investigate the possible effects of YSR on LMDs regulation and to clarify its mechanisms of intervention. In this study, YT, large‐leaf yellow tea aqueous extract (YAE), and large‐leaf yellow tea residue (YSR) were utilized as interventions in a LMDs model induced by HFD. Additionally, we evaluated their effects on serum lipid metabolism indices and explored potential mechanisms of intervention through transcriptome analysis. The results indicated that YT, YAE, and YSR interventions significantly decreased body weight and fasting glucose levels in mice, and moreover, serum lipid indices (including total cholesterol, triglycerides, LDL, insulin and leptin) along with hepatic lipid content exhibited a comparable reduction. Gene ontology and KEGG pathway analyses from RNA‐seq confirmed that YSR and YAE were primarily involved in lipid metabolism‐related signaling pathways. Both YSR and YAE interventions significantly upregulated genes involved in fatty acid oxidation (including Cyp4a , Acsl4 , Cpt1 , Ehhadh , Acot3 , and Acaa1b ). In addition, YSR significantly downregulated key genes in cholesterol synthesis (including Sqle , Tm7sf2 , Msmo1 , Nsdhl , and Dhcr24 ), while YAE upregulated genes related to bile acid synthesis ( Cyp7a1 ) expression. These findings underscore the potential of YT and its components in regulating lipid metabolism and suggest opportunities for developing high‐value products from YSR.