Secretion Of Epdr1 "batokine" By Aerobic Training Promotes Fat Burning And Browning In Obese Mice.

Brown and beige adipose tissue (BAT) promotes energy expenditure by thermogenesis mediated by uncoupling protein (UCP)-1. BAT have an endocrine system and secreted “batokines” play a crucial role in regulating metabolism. Ependymin-related protein 1 (EPDR1), which was recently identified as a novel batokine, is involved in development into a functional thermogenic adipocyte. However, the effects of habitual aerobic exercise on EPDR1 secretion of BAT remain unclear. PURPOSE: To clarify whether the secreted EPDR1 is associated with the fat burning and browning by habitual aerobic exercise in obese mice. METHODS: Eight-week-old ApoE-/- mice were used as an obese model and were randomly divided into the following two groups: sedentary control (ApoE-/- SED, n = 6) group and 16-wk voluntary wheel running aerobic exercise (ApoE-/- AT, n = 6) group. ApoE-/- mice of two groups were fed a high-fat diet during the experimental period. Age-matched C57BL/6 J wild-type mice were fed a normal chow and were used as a healthy sedentary control group (WT-SED, n = 6). RESULTS: Epididymal fat mass of the ApoE-/- SED group was significantly higher compared with WT-SED group (p < 0.05), and that of ApoE-/- AT group was significantly lower compared with ApoE-/- SED group (p < 0.05). Protein expression levels of PGC1-α, UCP-1, and EPDR1 in epididymal WAT (eWAT) were significantly higher in the ApoE-/- AT group as compared with ApoE-/- SED group (p < 0.05). Additionally, EPDR1 mRNA levels in interscapular BAT was higher in the ApoE-/- AT group as compared with ApoE-/-SED group. Plasma EPDR1 levels were higher in the ApoE-/- AT group as compared with ApoE-/-SED group (p < 0.05). Furthermore, EPDR1 protein expression levels in eWAT were positively correlated with PGC1-α (r = 0.431, p < 0.05) and UCP-1 (r = 0.325, p < 0.05) protein expression levels in eWAT. CONCLUSIONS: These findings suggest that the secreted EPDR1 is associated with the fat burning and browning via increase in UCP-1 protein expression by habitual aerobic exercise in obese mice. Supported by: Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (KAKENHI: 23 K24744 to M. Iemitsu)