Cardiovascular Characteristics of Zucker Fatty Diabetes Mellitus Rats, an Animal Model for Obesity and Type 2 Diabetes

Zucker fatty diabetes mellitus (ZFDM) rats harboring the missense mutation (fa) in a leptin receptor gene have been recently established as a novel animal model of obesity and type 2 diabetes (T2D). Here, we explored changes in cardiovascular dynamics including blood pressure and heart rate (HR) associated with the progression of obesity and T2D, as well as pathological changes in adipose tissue and kidney. There was no significant difference in systolic blood pressure (SBP) in ZFDM-Lepr^fa/fa (Homo) compared with ZFDM-Lepr^fa/+ (Hetero) rats, while HR and plasma adrenaline in Homo were significantly lower than Hetero. The mRNA expression of monocyte chemotactic protein-1 in perirenal white adipose tissue (WAT) from Homo was significantly higher than Hetero. Interscapular brown adipose tissue (BAT) in Homo was degenerated and whitened. The plasma blood urea nitrogen in Homo was significantly higher than Hetero. In summary, we demonstrated for the first time that HR and plasma adrenaline concentration but not SBP in Homo decrease with obesity and T2D. In addition, inflammation occurs in WAT from Homo, while whitening occurs in BAT. Further, renal function is impaired in Homo. In the future, ZFDM rats will be useful for investigating metabolic changes associated with the progression of obesity and T2D.