Transplantation of brown adipose tissue (BAT) from donor animals appeared to reduce weight gain in leptin-deficient Ob/Ob mice, presumably by enhancing the activity of endogenous brown fat, researchers reported.
In a series of studies in obesity and predisposed transgenic mice, BAT transplantation led to significant reductions in weight gain and decreased total body fat, lead researcherWanzhu Jin, PhD, of the Chinese Academy of Sciences, and colleagues, wrote in the journal Endocrinology.
“The results of the current study show that transplantation of BAT reduced adiposity and improved glucose homeostasis in the Ob/Ob mouse by significantly increasing energy expenditure,” the researchers wrote. “These beneficial effects were most likely mediated by the enhancement of endogenous BAT activity. These results may open new avenues to develop a novel treatment option to target obesity and its related diseases such as diabetes.”
BAT Transplant Mice Had Less Body Fat
Leptin deficient Ob/Ob mice, which are widely used for the study of obesity-induced diabetes, have a lower metabolic rate and hypothermia due to a defect in BAT function, the researchers wrote.
To determine whether BAT transplantation could reverse these traits, they transplanted brown fat from 6 week old C57B/L6 mice into the dorsal subcutaneous region of age and sex matched Ob/Ob mice.
The BAT transplantation mice were found to gain less weight than sham-operated control Ob/Ob mice and this difference was seen as early as 3 weeks after transplantation (47.8 ±2.2 g vs. 50.6±3.1 g, P<0.03). This trend persisted through 12 weeks post transplantation.
When the researchers measured body composition using computerized tomography, they found an 11% decrease in total body fat percentage in the BAT transplant mice compared with the control mice.
“Compared with control mice, there was a significant reduction of adipocyte size in subcutaneous fat but not in epididymal fat after BAT transplantation,” the researchers wrote.
There was no change in circulating IL-6 levels or IL-6 mRNA in epididymal fat, however, suggesting that BAT transplantation disrupted adipose tissue hypertrophy without altering inflammation.
BAT transplantation was also found to reverse hepatic steatosis, improve insulin sensitivity, and increase energy expenditures.
BAT transplantation into streptozotocin (STZ) induced type 1 diabetic mice resulted in complete reversal of most diabetic symptoms without exogenous insulin treatment and it reversed diet-induced obesity in another mouse model.
Adiponectin May Activate Endogenous BAT
In a series of experiments, the researchers showed that transplantation also enhanced the activity of endogenous BAT.
“Serum adiponectin levels and beta 3 adrenergic receptor expression levels in both subcutaneous and epididymal fat were significantly increased after BAT transplantation,” Jin and colleagues wrote. “Increase of plasma adiponectin after BAT transplantation might enhance activity of endogenous BAT to consume more triglyceride as consistent with previous reports.”
The findings suggest that activation of endogenous BAT, and not transplanted BAT, was primarily responsible for the improved metabolic profile seen in the transplanted mice, the researchers noted.
No difference in energy intake and no change in circulating leptin levels were detected following BAT transplantation, suggesting that the improved metabolic profile was not due to circulating leptin alone.
“Increasing evidence suggests that BAT might serve as a secretory organ,” the researchers wrote. “Similar to white adipose tissue, BAT could synthesize and secrete numerous hormones, such as FGF21, to regulate the whole body energy metabolism.”
The BAT transplant mice in the study showed significant reductions in circulating FGF21. In addition, circulating IL-6 was not altered following BAT transplantation, suggesting that additional inflammatory factors or other factors might be involved in energy metabolism, the researchers noted.
The finding that BAT transplantation reversed diabetes in type 1 and diet-induced obesity mouse models suggest that BAT secretes adipokines that work through insulin-independent pathways.
“As an endocrine organ, BAT could serve as a fascinating new potential therapeutic target for obesity and its related diseases,” the researchers wrote … “In the present study, we demonstrated that BAT transplantation ameliorated the body weight and body fat gain in Ob/Ob mice. This is the first study showing that BAT transplantation enhances the activity of endogenous BAT, eventually leading to the improvement of whole body energy metabolism and glucose homeostasis.”
Fecal microbiota transplantation (FMT) also known as a stool transplant is the process of transplantation of fecal bacteria from a healthy individual into a recipient. It has been proven to be a highly effective treatment for patients suffering from Clostridium difficile infection (CDI), which produces effects ranging from diarrhea to pseudomembranous colitis.