Dietary Polyphenols Target Mitochondrial Bioenergetics in the Liver-Adipose-Muscle Axis

Dietary polyphenols, bioactive compounds in fruits, vegetables, tea, cocoa, and herbs, improve metabolic health by targeting mitochondrial function in the liver, adipose tissue, and skeletal muscle. This review synthesizes evidence on how they enhance mitochondrial bioenergetics via shared and tissue-specific pathways, and how these effects are amplified through intertissue communication. Specifically, polyphenols modulate signaling along the liver-muscle axis (via hepatokines such as FGF21), the liver-fat axis (through adipokines like adiponectin and leptin), and the fat-muscle axis (involving myokines including irisin). Importantly, the gut microbiota contributes crucially by transforming polyphenols into active metabolites (e.g., urolithins), which further enhance mitochondrial function through the gut-liver, gut-adipose, and gut-muscle axes, collectively termed the "gut-X" axis. Collectively, polyphenols target mitochondria to enhance function in the liver, adipose tissue, and skeletal muscle. This coordinated multiorgan effect underscores their potential as a complementary dietary strategy for metabolic syndrome, obesity, and type 2 diabetes.