(A-D) To specifically downregulate (knock down) hepatic SHP (SHP-LKD), AAV-TBG-Cre, or AAV-TBG-GFP as a control, was injected into SHP-floxed (SHP f/f) mice. Six weeks after injection, the mice were fasted for 4 h and sacrificed. (A) Experimental approach (top) and liver and intestinal SHP protein levels measured by immunoblotting (bottom). (B) Global expression changes in microRNA expression displayed in a volcano plot. (C) List of miRs with levels up-regulated (left panel) or down-regulated (right panel) by 1.5 fold or more with P values <0.05. (D) Relative levels of miR-210 with the mean control level set to 1. (E) C57BL/6 mice were injected with adenovirus expressing GFP or SHP and sacrificed 3 weeks later. SHP levels detected by IB (left) and relative miR-210 levels with the mean GFP value set to 1 (right). (A, D, E) Statistical significance was determined by the Student’s t-test, standard deviation (SD, n=5), ** p < 0.01.