Reduced adiposity by compensatory WAT browning upon iBAT removal in mice

Highlights: • Prolonged time course for cold exposure was utilized to elucidate dynamic changes in BAT and in WAT browning in mice. • Loss of classic iBAT enhanced WAT browning due to compensatorily increased sympathetic WAT input in mice. • Significantly reduced adiposity in the iBAT removal group compared with the control group in mice. The strong effects of classic brown adipose tissue (BAT) and recruited beige adipocytes in treatment of obesity and metabolic syndrome have been attracting increasing research interest. Cold treatment is an effective, convenient approach to stimulate BAT activity and induce white adipose tissue (WAT) browning. Here, we utilized prolonged cold exposure (from 2 h to 2 weeks in a 4° cold chamber) to elucidate dynamic changes in BAT and in WAT browning during acute and chronic cold exposure in mice. BAT mass decreased quickly, with reduced lipid droplet sizes within 8 h of cold exposure owing to the utilization of BAT pre-storage triglycerides, and subsequently increased during prolonged cold exposure. These dynamic morphological changes in BAT were confirmed by gene expression changes in ADRB3 and PGC1α, while UCP1 and ELOVL3 expression was continuously up-regulated throughout the entire cold exposure period. Additionally, cold treatment increased BAT secretion of FGF21, which has been reported to activate beige adipocyte formation. Thus, to illustrate potential crosstalk between secreted BAT proteins (so-called BATokines) and beige adipogenesis during cold stress, we performed an interscapular BAT (iBAT) removal experiment in mice. Surprisingly, loss of classic iBAT enhanced WAT browning due to compensatorily increased sympathetic WAT input. Unexpectedly, we observed significantly reduced adiposity in the iBAT removal group compared with the control group. These results further suggest that WAT browning plays an important role in whole-body energy metabolism during cold acclimation, even without iBAT. Furthermore, our data imply that enhanced WAT browning may be an efficient therapeutic tool to combat obesity and related syndromes.