Epigallocatechin gallate and lipid metabolism: intestinal fate, metabolite clusters, and regulatory mechanisms

Epigallocatechin gallate (EGCG), a principal bioactive constituent of tea, exhibits substantial activity in regulating lipid metabolism. Although EGCG has been extensively studied, an integrated synthesis of its actions across lipid metabolic pathways remains lacking. This review summarizes the intestinal metabolic fate of EGCG and delineates its regulatory mechanisms in fatty acids (FAs), triglycerides, and cholesterol metabolism. By integrating evidence from multiple perspectives, we provide a mechanistic rationale and assess the translational potential of EGCG-based nutritional interventions for diseases associated with lipid dysregulation. EGCG is enzymatically metabolised in the small intestine and liver, and the colonic microbiota then transforms it into lower-molecular-weight, more readily absorbable metabolites, including phenyl-γ-valerolactones (PVLs) and phenolic acids. These metabolites may act in concert with EGCG to modulate key lipid metabolic axes. Specifically, EGCG activates AMP-activated protein kinase (AMPK), leading to decreased de novo lipogenesis (DNL) and enhanced fatty acid oxidation (FAO); links to the induction of lipid droplet–targeted lipophagy, which reduces intracellular triglyceride burden; and interacts with phosphatidylcholine to disrupt cholesterol’s mixed-micelle solubilization, thereby inhibiting intestinal cholesterol absorption. The combined impact of EGCG and its derived metabolites across these pathways suggests a coordinated mechanistic network underlying its effects on lipid metabolism. Finally, we highlight that EGCG’s system-level effects are strongly shaped by microbiota-derived metabolites, which may act as key effectors across organs and targets. We conclude by outlining priorities for future research. Regulatory effects of epigallocatechin gallate (EGCG) on lipid metabolism and molecular mechanisms. • Gut-first EGCG fate reframes lipid actions as a host–microbiome metabolite cluster. • EGCG and its active metabolites affect the metabolism of LCFAs through β-oxidation and of SCFAs by intestinal flora. • EGCG defines AMPK-mTOR lipophagy and esterification blockade as key routes for lowering triglycerides. • EGCG demonstrates the ability to regulate cholesterol homeostasis by means of micelles, NPC1L1 protein, and bile acid excretion. • The regulatory role of EGCG in lipid metabolism forms a network with AMPK as a key hub.