Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T₃ and T₄, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased β3-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT.

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.

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.

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

Alliin (S-allyl cysteine sulfoxide) is a bioactive sulfoxide compound derived from garlic. To evaluate the preventive effect of alliin against metabolic risk factors in diet induced obese (DIO) mice, we treated the C57BL/6J DIO mice with drinking water with or without alliin (0.1 mg/ml) for 8 weeks. Results showed that alliin had no significant effect on the body weight, adiposity or energy balance. However, alliin treatment enhanced glucose homeostasis, increased insulin sensitivity and improved the lipid profile in the DIO mice. This was, at least partly, attributable to alliin induced modulation of the intestinal microbiota composition, typically decreasedLachnospiraceaeand increasedRuminococcaceae. From above, we conclude that alliin has nutraceutical or even medicinal potential in prevention of diabetes and lipid metabolic disorders.