Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation

Abstract

ObjectiveDietary fibre has beneficial effects on energy metabolism, and the majority of studies have focused on short-chain fatty acids produced by gut microbiota. Ginseng has been reported to aid in body weight management, however, its mechanism of action is not yet clear. In this study, we focused on the potential modulating effect of ginseng on gut microbiota, aiming to identify specific strains and their metabolites, especially long-chain fatty acids (LCFA), which mediate the anti-obesity effects of ginseng.DesignDb/db mice were gavaged with ginseng extract (GE) and the effects of GE on gut microbiota were evaluated using 16S rDNA-based high throughput sequencing. To confirm the candidate fatty acids, untargeted metabolomics analyses of the serum and medium samples were performed.ResultsWe demonstrated that GE can induce Enterococcus faecalis, which can produce an unsaturated LCFA, myristoleic acid (MA). Our results indicate that E. faecalis and its metabolite MA can reduce adiposity by brown adipose tissue (BAT) activation and beige fat formation. In addition, the gene of E. faecalis encoding Acyl-CoA thioesterases (ACOTs) exhibited the biosynthetic potential to synthesise MA, as knockdown (KD) of the ACOT gene by CRISPR-dCas9 significantly reduced MA production. Furthermore, exogenous treatment with KD E. faecalis could not reproduce the beneficial effects of wild type E. faecalis, which work by augmenting the circulating MA levels.ConclusionsOur results demonstrated that the gut microbiota-LCFA-BAT axis plays an important role in host metabolism, which may provide a strategic advantage for the next generation of anti-obesity drug development.

Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation

“…Recent findings suggest that the metabolic activities of enteric microbiota may affect the levels of long-chain fatty acids [47]. Oral gavage of Enterococcus faecalis has been reported to affect a variety of long-chain fatty acids, including palmitoleic [48]. In addition, increased palmitoleic acid was previously observed in mice fed gut Bifidobacterium breve [49] and Lactobacillus rhamnosus LA68 [50].…”

Intestinal-derived FGF15 preserves muscle and bone mass following sleeve gastrectomy

“…Enterococcus was the main driver of difference between the FGF15 INT-KO Sham and VSG groups at the genus level ( Figure 6D). Increase in Enterococcus species in the gut has been linked to decreased adiposity as a result of increased energy expenditure (Quan et al, 2019). A recent study showed that a probiotic cocktail of Lactobacillus and Enterococcus prevented dietinduced inflammation and leaky gut by increasing bile acid hydrolase activity (Ahmadi et al, 2020).…”

Role of gut microbiota in identification of novel TCM-derived active metabolites

“…Branched chain amino acids (BCAAs), such as leucine (Leu), isoleucine (Ile), and valine (Val), work both as the substrates for anabolism of nitrogenous compounds and as signaling molecules regulating energy homeostasis via multiple signaling networks, including the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway (Nie et al, 2018). Gut microbiota also participates in fermentation of BCAA and generates a complex mixture of metabolites, including ammonia, SCFAs, and branched-chain fatty acids (valerate, isobutyrate, and isovalerate).…”

“…The changed gut microbiota composition by TCM herbs administration may contribute to the ameliorative effects on abnormal lipids metabolism (Huang et al, 2019;Zhang et al, 2019a). On the other hand, ginseng extract can enrich Enterococcus faecalis that produces an unsaturated long chain fatty acid, myristoleic acid (MA), leading to reducing adiposity by activation of brown adipose tissue (BAT) and formation of beige fat (Quan et al, 2019). Therefore, modulation of gut microbiota bacteria by TCM herbs may produce optimal amounts of beneficial lipid metabolites, which is an effective strategy for promotion of well-being in hosts.…”