Skeletal muscle provides a pro-browning microenvironment for transplanted brown adipose tissue to maintain its effect to ameliorate obesity in ob/ob mice.

Abstract

Brown adipose tissue (BAT) transplantation is a promising means of increasing whole-body energy metabolism to ameliorate obesity. However, the changes in BAT following transplantation and the effects of the microenvironment of the recipient site on graft function have yet to be fully characterized. Therefore, we aimed to determine the effects of transplanting BAT from C57BL/6 mice into the dorsal subcutaneous region or deep to the quadriceps femoris muscle of leptin-deficient ob/ob mice. Subcutaneously transplanted BAT lost features of BAT and demonstrated greater inflammatory cell infiltration and more oil cysts 16weeks following transplantation. By contrast, the sub-muscularly transplanted BAT maintained features of BAT and was more highly vascularized. Interestingly, sub-muscular BAT transplantation led to a significant increase in oxygen consumption and less inflammation in subcutaneous fat, which was associated with long-term reductions in insulin resistance and body mass gain, whereas the subcutaneous transplants failed after 16weeks. These results demonstrate that the beneficial effects of BAT transplantation depend upon the microenvironment of the recipient site. Skeletal muscle may provide a microenvironment that maintains the inherent features of BAT grafts over a long period of time, which facilitates a reduction in obesity and improvements in glucose homeostasis.