Theabrownin from Fu Brick tea ameliorates high-fat induced insulin resistance, hepatic steatosis, and inflammation in mice by altering the composition and metabolites of gut microbiota.

Fu Brick tea belongs to fermented dark tea, which is one of the six categories of tea. Fu Brick tea has been reported to reduce adiposity and has beneficial effects in the treatment of hypercholesterolemia and cardiovascular disease. Theabrownin (TB) is one of the pigments with the most abundant content in Fu Brick tea. TB has also been reported to have lipid-lowering effects, but its mechanism remains unclear. We found that TB could effectively reduce the insulin resistance and fat deposition induced by a high fat diet (HFD), decrease inflammation in the liver, improve intestinal integrity, and reduce endotoxins in circulation. Further studies showed that TB increased the abundance of Verrucomicrobiota and reduced the abundance of Firmicutes and Desulfobacterota in the intestinal tract of obese mice. The alteration of gut microbiota is closely linked to the metabolic phenotype after TB treatment through correlation analysis. Moreover, TB changed the gut microbial metabolites including L-ornithine, α-ketoglutarate, and glutamine, which have also been found to be upregulated in the liver after TB intervention. In vitro, L-ornithine, α-ketoglutarate, or glutamine significantly reduced lipopolysaccharide (LPS)-induced inflammation in macrophages. Therefore, our results suggest that TB can reduce adiposity, systemic insulin resistance, and liver inflammation induced by a HFD through altering gut microbiota and improving the intestinal tight junction integrity. The metabolites of gut microbiota might also play a role in ameliorating the HFD-induced phenotype by TB.

Theabrownin ameliorates liver inflammation, oxidative stress, and fibrosis in MCD diet-fed C57BL/6J mice.

Introduction: Nonalcoholic steatohepatitis (NASH), also known as metabolic steatohepatitis, is a clinical syndrome with pathological changes like alcoholic hepatitis but without a history of excessive alcohol consumption. NASH is closely related to metabolic disorders such as obesity, insulin resistance, type 2 diabetes mellitus, and hyperlipidemia. Its main characteristics are hepatocyte steatosis with hepatocyte injury and inflammation. In severe cases, it can develop into liver cirrhosis. At present, there is no special treatment for NASH. Theabrownin (TB) is the main pigment substance in fermented tea. Theabrownin has beneficial effects on lipid metabolism and intestinal flora. However, the effect of theabrownin on NASH has not been studied. Methods: This study was aimed at exploring the effects of theabrownin from Fuzhuan brick tea on NASH. 8-week-old mice were randomly assigned to three groups and fed with chow diet (CD), methionine and choline sufficient (MCS) diet (MCS Ctrl), which is a Methionine/choline deficient (MCD) control diet, and MCD diet. After 5 weeks of feeding, the MCD group mice were randomly divided into two groups and were gavaged with double distilled water (MCD Ctrl) or theabrownin (MCD TB) (200mg/kg body weight, dissolved in double distilled water) every day for another 4 weeks respectively, while continuing MCD diet feeding. Results: We found that theabrownin treatment could not improve liver mass loss and steatosis. However, theabrownin ameliorated liver injury and decreased liver inflammatory response. Theabrownin also alleviated liver oxidative stress and fibrosis. Furthermore, our results showed that theabrownin increased hepatic level of fibroblast growth factor 21 (FGF21) and reduced the phosphorylation of mitogen-activated protein kinase p38 in MCD diet-fed mice.

The Role of Palmitoleic Acid in Regulating Hepatic Gluconeogenesis through SIRT3 in Obese Mice.

Hepatic gluconeogenesis is a crucial process to maintain glucose level during starvation. However, unabated glucose production in diabetic patients is a major contributor to hyperglycemia. Palmitoleic acid is a monounsaturated fatty acid (16:1n7) that is available from dietary sources. Palmitoleic acid exhibits health beneficial effects on diabetes, insulin resistance, inflammation, and metabolic syndrome. However, the mechanism by which palmitoleate reduces blood glucose is still unclear. SIRT3 is a key metabolism-regulating NAD+-dependent protein deacetylase. It is known that fasting elevates the expression of SIRT3 in the liver and it regulates many aspects of liver's response to nutrient deprivation, such as fatty acid oxidation and ketone body formation. However, it is unknown whether SIRT3 also regulates gluconeogenesis. Our study revealed that palmitoleic acid reduced hepatic gluconeogenesis and the expression of SIRT3 under high-fat diet conditions. Overexpression of SIRT3 in the liver and hepatocytes enhanced gluconeogenesis. Further study revealed that SIRT3 played a role in enhancing the activities of gluconeogenic enzymes, such as PEPCK, PC, and MDH2. Therefore, our study indicated that under a high-fat diet, palmitoleic acid decreased gluconeogenesis by reducing enzymatic activities of PEPCK, PC, and MDH2 by down-regulating the expression of SIRT3.