Objective: Dietary 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. Design: Db/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. Results: We 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. Conclusions: Our 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.

Overweight and obesity have become a world-wide problem. However, effective intervention approaches are limited. Brown adipose tissue, which helps maintain body temperature and contributes to thermogenesis, is dependent on uncoupling protein1. Over the last decade, an in-creasing number of studies have found that activating brown adipose tissue and browning of white adipose tissue can protect against obesity and obesity-related metabolic disease. Brown adipose tissue has gradually become an appealing therapeutic target for the prevention and re-versal of obesity. However, some important issues remain unresolved. It is not certain whether increasing brown adipose tissue activity is the cause or effect of body weight loss or what the risks might be for sympathetic nervous system-dependent non-shivering thermogenesis. In this review, we comprehensively summarize approaches to activating brown adipose tissue and/or browning white adipose tissue, such as cold exposure, exercise, and small-molecule treatment. We highlight the functional mechanisms of small-molecule treatment and brown adipose tissue transplantation using batokine, sympathetic nervous system and/or gut microbiome. Finally, we discuss the causality between body weight loss induced by bariatric surgery, exercise, and brown adipose tissue activity.

Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter‐organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose‐regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK‐ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.

Alcohol plays an important role in medical treatment, culture, and social interaction. However, excessive alcohol consumption or improper alcohol intake patterns can lead to serious damage to health.

PA treatment effectively and safely protected against obesity via the BAT-UCP1 axis. PA has therapeutic potential for treating obesity and type II diabetes.