The Great Roundleaf Bat (Hipposideros armiger) as a Good Model for Cold-Induced Browning of Intra-Abdominal White Adipose Tissue

Background

Inducing beige fat from white adipose tissue (WAT) is considered to be a shortcut to weight loss and increasingly becoming a key area in research into treatments for obesity and related diseases. However, currently, animal models of beige fat are restricted to rodents, where subcutaneous adipose tissue (sWAT, benign WAT) is more liable to develop into the beige fat under specific activators than the intra-abdominal adipose tissue (aWAT, malignant WAT) that is the major source of obesity related diseases in humans.

Methods

Here we induced beige fat by cold exposure in two species of bats, the great roundleaf bat (Hipposideros armiger) and the rickett''s big-footed bat (Myotis ricketti), and compared the molecular and morphological changes with those seen in the mouse. Expression of thermogenic genes (Ucp1 and Pgc1a) was measured by RT-qPCR and adipocyte morphology examined by HE staining at three adipose locations, sWAT, aWAT and iBAT (interscapular brown adipose tissue).

Results

Expression of Ucp1 and Pgc1a was significantly upregulated, by 729 and 23 fold, respectively, in aWAT of the great roundleaf bat after exposure to 10°C for 7 days. Adipocyte diameters of WATs became significantly reduced and the white adipocytes became brown-like in morphology. In mice, similar changes were found in the sWAT, but much lower amounts of changes in aWAT were seen. Interestingly, the rickett''s big-footed bat did not show such a tendency in beige fat.

Conclusions

The great roundleaf bat is potentially a good animal model for human aWAT browning research. Combined with rodent models, this model should be helpful for finding therapies for reducing harmful aWAT in humans.