Brown Adipose Tissue Transplantation Reverses Obesity in Ob/Ob Mice

Abstract

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.

Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism

“…Consistent with previous studies (28,33,43), we demonstrate strong ameliorating effects on metabolic disturbance by BAT transplantation. This is the first report to our knowledge that BAT transplantation affects metabolic regulation using an animal model of BAT dysfunction.…”

“…Further investigation is required to elucidate of the regional regulation of transplanted BAT. Regarding the regulatory factors of systemic energy metabolism by BAT transplantation, participation of secreted factors, such as fibroblast growth factor 21 (FGF21), IL-6, and insulin-like growth factors 1 (IGF-1), has been proposed (28,43,44). While we did not investigate these factors in the present study, it is also possible that BH4 itself or BH4-induced NO and NA participate in the beneficial effects on metabolism after the BAT transplantation.…”

“…Regarding the area of the BAT graft, Stanford et al reported that, compared with these beneficial effects of BAT transplantation into the visceral cavity, transplantation of BAT into the subcutaneous cavity of mice did not result in changes in glucose tolerance (28). However, there have been reports that beneficial metabolic effects were obtained by BAT transplantation into the subcutaneous region (33,43). Further investigation is required to elucidate of the regional regulation of transplanted BAT.…”

Identification and characterization of a supraclavicular brown adipose tissue in mice

“…To determine whether scBAT improves glucose metabolism in vivo, we utilized a transplantation model. Previous studies have shown that transplantation of iBAT into adult mice significantly improved glucose homeostasis and thermoregulation, demonstrating the beneficial metabolic effects of iBAT (29,30). Here, we examined whether transplantation of scBAT into healthy adult mice has the same effect as transplantation of iBAT.…”

The color of fat and its central role in the development and progression of metabolic diseases

“…BAT transplantation in ob/ob mice decreased weight gain as well as total and hepatic fat, but also increased the expressions of β-adrenergic receptors and gene related fatty acid oxidation related in subcutaneous and epididymal (EP) WAT [85]. Thus, the differentiation of WAT into BAT or BeAT has emerged as a promising way to induce energy expenditure and has been proposed as a possible tool to counteract obesity and insulin resistance.…”