Fasting and refeeding signals modulate hepatic Bmal1 expression via glucagon and insulin, respectively.
A, imaging analysis of the hepatic activity of adenoviral luciferase reporter driven by Bmal1 promoter (Bmal1-Luc) in mice fed ad libitum at ZT0, ZT6, ZT12, and ZT18. Luciferase activity was normalized to co-infected Ad-RSV-β-gal reporter activity in the liver (right, n = 3 per group). B, in vivo imaging analysis of Ad-Bmal1-Luc reporter activity in mice fed ad libitum (Ad lib), 24-h fasted (from Day1-ZT10), or 2-h refed (from Day2-ZT8). C, imaging analysis of the hepatic activity of Bmal1-Luc in mice fed ad libitum AND fasted for 22 h (from ZT12) followed by 2-h injection of saline (Ctrl) or insulin (INS, 0.5 units/kg). D, bar graph showing relative Ad-Bmal1-Luc activity in B and C. Luciferase activity was normalized to co-infected Ad-RSV-β-gal reporter activity in the liver (n = 3 per condition, * as compared with Ad lib group, # as compared with fasted group, ns, no significance). E, the effects of fasting (from Day1-ZT10) and refeeding (from Day2-ZT8) on hepatic mRNA levels of Bmal1 (n = 3). F, quantitative PCR analysis of Bmal1 mRNA levels in mice fed ad libitum, fasted for 22 h (from ZT12) followed by 2-h injection of saline (Ctrl) or insulin (0.5 units/kg). G, in vivo imaging analysis of Ad-Bmal1-Luc reporter activity in mice fed ad libitum, fasted for 4, 26, and 28 h (from Day1-ZT12), or refed for 2 and 4 h (from Day2-ZT12) relative to Fig. 1. H and I, quantitative PCR analysis of Bmal1 mRNA level (H) and immunoblot analysis of BMAL1 protein amounts (left, n = 5) and densitometry analysis of BMAL1 protein (right, I) in mice injected with glucagon (GLU, 100 μg/kg) for 4 h (from ZT4) or saline (Ctrl). p-CREB, phospho-CREB. Data are represented as mean ± S.E., *or # p < 0.05, **or ## p < 0.01.