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.

Brown adipose tissue transplantation improves whole-body energy metabolism

Significance: In the current study, we show that brown adipose tissue (BAT) activity is dramatically reduced in a dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) rat when compared with a normal control rat. Importantly, the key features of PCOS (such as insulin resistance and irregular estrous cycle) are alleviated after BAT transplantation. Mechanistically, transplanted BAT enhances endogenous BAT activity and thereby increases the circulating adiponectin level, which was lower in both the PCOS patient and PCOS rat model. Furthermore, exogenous adiponectin protein administration recapitulates beneficial effects from BAT transplantation in a PCOS rat. Taken together, these data highlight the important role of BAT in the development of PCOS and that BAT-induced adiponectin might open up a new way in the treatment of PCOS.

Significance: Uncoupling protein 1 (UCP1) is responsible for brown adipose tissue-mediated thermogenesis and plays a critical role in protecting against cold and regulating energy homeostasis. Modern pigs lack functional UCP1, which makes them susceptible to cold and prone to fat deposition and results in neonatal mortality and decreased production efficiency. In the current study, a CRISPR/Cas9-mediated homologous recombination-independent approach was established, and mouse adiponectin-UCP1 was efficiently inserted into the porcine endogenous UCP1 locus. The resultant UCP1 KI pigs showed an improved ability to maintain body temperature, decreased fat deposition, and increased carcass lean percentage. UCP1 KI pigs are a potentially valuable resource for the pig industry that can improve pig welfare and reduce economic losses.

Increasing energy expenditure through activation of brown adipose tissue (BAT) is a critical approach to treating obesity and diabetes. In this study, rutin, a natural compound extracted frommulberry and a drug used as a capillary stabilizer clinically formany years without any side effects, regulated whole‐body energymetabolism by enhancing BAT activity. Rutin treatment significantly reduced adiposity, increased energy expenditure, and improved glucose homeostasis in both genetically obese (Db/Db) and diet‐induced obesity (DIO) mice. Rutin also induced brown‐like adipocyte (beige) formation in subcutaneous adipose tissue in both obesity mouse models. Mechanistically, we found that rutin directly bound to and stabilized SIRT1, leading to hypoacetylation of peroxisome proliferator‐activated receptor γ coactivator‐1α protein, which stimulated Tfam transactivation and eventually augmented the number of mitochondria and UCP1 activity in BAT. These findings reveal that rutin is a novel small molecule that activates BAT and may provide a novel therapeutic approach to the treatment of metabolic disorders.—Yuan, X., Wei, G., You, Y., Huang, Y., Lee, H. J., Dong, M., Lin, J., Hu, T., Zhang, H., Zhang, C., Zhou, H., Ye, R., Qi, X., Zhai, B., Huang, W., Liu, S., Xie, W., Liu, Q., Liu, X., Cui, C., Li, D., Zhan, J., Cheng, J., Yuan, Z., Jin, W. Rutin ameliorates obesity through brown fat activation. FASEB J. 31, 333–345 (2017) www.fasebj.org

Pigs lack functional uncoupling protein 1 (UCP1) making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism(s) enabling such adaptation are currently unknown. Here, we show that this resistance is not dependent on shivering, but rather depends on UCP3 and white adipose tissue (WAT) browning. In two cold-resistant breeds (Tibetan and Min), but not a cold-sensitive breed (Bama), WAT browning was induced after cold exposure. Beige adipocytes from Tibetan pigs exhibited greater oxidative capacity than those from Bama pigs. Notably, UCP3 expression was significantly increased only in cold-resistant breeds, and knockdown of UCP3 expression in Tibetan adipocytes phenocopied Bama adipocytes in culture. Moreover, the eight dominant pig breeds found across China can be classified into cold-sensitive and cold-resistant breeds based on the UCP3 cDNA sequence. This study indicates that UCP3 has contributed to the evolution of cold resistance in the pig and overturns the orthodoxy that UCP1 is the only thermogenic uncoupling protein.