Eurotium cristatum from Fu Brick Tea Promotes Adipose Thermogenesis by Boosting Colonic Akkermansia muciniphila in High-Fat-Fed Obese Mice

Abstract

This study investigated the potential fat-thermogenic effects of Eurotium cristatum, and elucidated the underlying mechanisms. The 12-week administration of E. cristatum in HFD-fed obese mice reduced body weight and improved glucolipid metabolism disorders. The administration of E. cristatum also efficiently promoted thermogenesis by increasing the expression of UCP1 and PRDM16 in both interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of HFD-fed mice. Furthermore, E. cristatum shaped the gut microbiome by increasing the abundance of Parabacteroides and Akkermansia muciniphila, and also elevated the levels of cecal short-chain fatty acids, particularly propionate and acetate. Of note, A. muciniphila was highly negatively correlated with body weight gain (r = -0.801, p < 0.05) and the iWAT index (r = -0.977, p < 0.01), suggesting that A. muciniphila may play an important role in the thermogenic mobilization induced by E. cristatum. Continuous supplementation with A. muciniphila suppressed adipose accumulation, improved glucolipid metabolism, and enhanced the thermogenic activity of iWAT and iBAT. Collectively, our results propose that boosted A. muciniphila acts as a key microbe in tea-derived probiotic E. cristatum-mediated fat-thermogenic and anti-obesity effects.

Keywords: Akkermansia muciniphila; Eurotium cristatum; Fu brick tea; fat thermogenesis; gut microbiota.

Figure 1

Curves of body weight (A). The gain in body weight (B). Food intake (C). OGTT (D). ITT (E). AUC of OGTT, ITT (F,G). Levels of TG, TC, LDL-C, and HDL-C (H–K). Different letters are used to denote statistical significance (p < 0.05) among groups.

Figure 2

The weight of iBAT, rWAT, eWAT, iWAT, and the liver (A). Tissue index of iBAT and iWAT (B,C). H&E staining of iWAT, iBAT, and eWAT (D). Thermogenic and mitochondrial gene expression in iBAT (E). PRDM16 and UCP1 immunofluorescent staining in iBAT (F) and iWAT (G). Adipocyte histology was observed at a magnification of 20×. Different letters are used to denote statistical significance (p < 0.05) among groups.

Figure 3

The total concentration of SCFAs (A) and the concentration of 6 different kinds of SCFA (B). Different letters are used to denote statistical significance (p < 0.05) among groups.

Figure 4

Alpha-diversity including Sobs index, Chao index, PCoA, and NMDS (A–D), and hierarchical clustering (E) of microbiota communities.

Figure 5

Phylum-level analysis of gut microbiota (A). Relative abundances of Bacteroidetes and Firmicutes (B). Genus-level heatmap of gut microbiota (C). Relative abundances of Anaerotruncus, Lachnoclostridium, Parabacteroides, and A. muciniphila (D–G). Different letters are used to denote statistical significance (p < 0.05) among groups.

Figure 6

The relationship between obesity-related parameters and gut microbiota at phylum and genus levels (A,B). * p < 0.05, ** p < 0.01.

Figure 7

Curves of body weight (A). The gain in body weight (B), Food intake (C), OGTT and ITT (D,E). Levels of TG, TC, LDL-C, and HDL-C (F–I). Different letters are used to denote statistical significance (p < 0.05) among groups.

Figure 8

The weight of iBAT, rWAT, eWAT, iWAT, and the liver (A). H&E staining of iWAT, iBAT, and eWAT (B). Thermogenic and mitochondrial gene expression in iWAT (C). PRDM16 and UCP1 immunofluorescent staining in iWAT (D). Thermogenic and mitochondrial gene expression in iBAT (E). PRDM16 and UCP1 immunofluorescent staining in iBAT (F). Adipocyte histology was observed at a magnification of 20×. Different letters are used to denote significance (p < 0.05) among groups.