White and Brown Adipose Grafts: An Approach to Correct Reproductive, Metabolic, and Renal Deficits in Black and Tan Brachyury (BTBR) Obese Mice

Transplantation of white adipose tissue (WAT) and brown adipose tissue (BAT) has emerged as a promising therapeutic strategy for reversing metabolic disorders without the need for sustained administration of exogenous agents. WAT functions as a key endocrine organ involved in energy homeostasis, while BAT is a thermogenic tissue critical for thermoregulation. The Black and Tan Brachyuric (BTBR) obese mouse model closely mimics key features of obesity, type 2 diabetes mellitus (T2DM), and diabetic kidney disease (DKD), including hyperglycemia, insulin resistance, hypometabolism, and subfertility. Using the protocol presented below, combined transplantation of WAT and BAT derived from BTBR wild-type and heterozygous donors into BTBR obese recipients resulted in the reversal of subfertility, attenuation of weight gain, normalization of glycemic control, and improvement of renal parameters. Notably, renal hypertrophy and apoptosis were reduced, while podocyte numbers were preserved. These findings suggest that combined WAT and BAT transplantation may represent an alternative therapeutic strategy for the treatment of T2DM, with concurrent benefits in mitigating DKD and obesity. Furthermore, this approach may aid in increasing the number of viable BTBR obese mice within vivarium colonies. Further investigation into the underlying mechanisms may facilitate the clinical translation of this intervention.