Roles of Gut Microbiota Metabolites and Circadian Genes in the Improvement of Glucose and Lipid Metabolism in KKAy Mice by Theabrownin

Theabrownin (TB), a prominent pigment in fermented dark tea, exhibits beneficial effects on adiposity reduction. Our study revealed that TB derived from Fu brick tea significantly lowered fasting blood glucose levels and insulin resistance in obese/diabetic KKAy mice. Furthermore, TB demonstrated potent anti-inflammatory effects in the liver, adipose tissue, and intestines, as well as enhancing intestinal integrity. Additionally, TB was found to inhibit hepatic gluconeogenesis and promote fatty acid oxidation. Notably, TB altered gut metabolites, particularly l-palmitoylcarnitine, which showed an elevation in serum, liver, and adipose tissue following TB intervention. l-Palmitoylcarnitine reduced gluconeogenesis in primary hepatocytes and decreased lipid deposition in both primary hepatocytes and 3T3-L1 adipocytes <i>in vitro</i>. However, these effects were abolished when the circadian gene Period 3 (Per3) was knocked down. Our findings suggest that l-palmitoylcarnitine may play a crucial role in improving TB-mediated glucose homeostasis and lipid metabolism by regulating Per3.