In addition to the energy-storing white adipose tissue (WAT), mammals possess brown adipose tissue (BAT) that burns fat to release heat for thermogenesis. BAT is abundant in mammals with high thermoregulatory demands, such as small mammals and the neonates of large mammals [1]. BAT was previously believed to be present only in small mammals and human infants. However, active BAT was also demonstrated in adult humans in the early 1990s [2-3]. Interestingly, in adult humans, BAT activity shows an inverse correlation with body mass index (BMI) and the percentage of body fat [4-5]. These findings indicate that BAT may play an important role in whole-body energy metabolism, although direct evidence is still lacking. In the current study, we found that BAT transplantation improved whole-body energy metabolism and increased insulin sensitivity. In addition, BAT transplantation not only prevented high-fat diet (HFD)-induced weight gain but also reversed preexisting obesity. Furthermore, we showed that these effects were BAT-transplantation specific, as transplantation of other tissues did not produce similar effects. To investigate the possible beneficial effects of BAT on HFD-induced obesity, we performed BAT transplantations. BAT was dissected from strain-, sex-and agematched donor mice and was subcutaneously transplanted into the dorsal interscapular region (Supplementary information, Figure S1M) of recipient mice (Figure 1A-1I). The recipient mice were then fed an HFD, which began immediately after the transplantation and continued for 20 weeks. BAT transplantation strikingly reduced HFD-induced weight gain in the transplanted mice compared with sham-operated control mice that were also fed an HFD. This effect appeared as early as 4 weeks post BAT transplantation and reached a maximum at the end of the study (Figure 1A). The weight change was accompanied by significant post-BAT-transplantation reductions in the weights of large organs, such as the liver and subcutaneous adipose tissue (Supplementary information, Figure S1D). Moreover, the whole-body fat percentage was reduced (Figure 1B) despite the absence of significant changes in energy intake or energy absorption after BAT transplantation (Supplementary information, Figure S1A-S1B).

BAT is a major organ that can generate large amounts of heat; it is responsible for at least 60% of non-shivering thermogenesis in cold-acclimated animals [6]. Therefore, we investigated whether BAT transplantation produced any effect on thermogenesis. We demonstrated that BAT transplantation not only significantly increased the core body temperature of animals under thermoneutral conditions (Figure 1C), but also greatly increased the core body temperature of animals that were challenged by exposure to cold conditions (4 C, 6 h)(Figure 1C-1D). This elevation in body temperature was linked to an increase in energy metabolism, as evidenced by a large increase in oxygen consumption (Figure 1E) that was not accompanied by a significant change in the respiratory quotient (RQ)(Supplementary information, Figure S1E). Notably, the results of gene expression analyses also support the above observations: BAT transplantation significantly increased the expression of fatty acid oxidation-related genes, such as MCAD, PPARα, PGC1α, CPT1β, and UCP1, in endogenous BAT and muscle tissue (Figure 1F and Supplementary information, Figure S1I). However, similar changes were not observed in epididymal or subcutaneous fat (Supplementary information, Figure S1F-S1G). A previous research has suggested that a reduction in physical activity occurs in mouse models of …