Effect of Fasting and Deoxycholic Acid Feeding in Xbp1-Knockout and Xbp1-Flox Control Mice
Session Number
C14
Advisor(s)
Richard Green, Northwestern University
Location
B-131 Grainger
Start Date
28-4-2016 10:15 AM
End Date
28-4-2016 10:40 AM
Abstract
The unfolded protein response (UPR) is a protective response which helps the cell adapt to intracellular stressors. Recent data indicates that the UPR affects hepatic lipid and glucose metabolism. This study analyzes how the individual and combined effects of bile acid feeding followed by fasting or non-fasting periods affect phosphorylated inositol requiring enzyme 1 alpha (IRE1α), a UPR protein. Cre+ X-box binding protein 1 (Xbp1) knock-out mice (lacking hepatic Xbp1) and Cre- mice (containing hepatic Xbp1) were either fed chow or 0.3% deoxycholic acid (a bile salt) for three days. After feeding, the mice were either left non-fasted or were fasted for 4 hours before sacrifice. Western blots indicate that phosphorylated- IRE1α is prominent in 4 hours fasted DCA-fed Cre+ mice and 4 hours fasted chow-fed Cre+ mice, which may be due to loss of suppression by XBP1 in knockout mice. Further testing will examine how IRE1α alters with different fasting periods in chow and DCA-fed mice. Additionally, XBP1 will be studied to analyze its interaction with its upstream target, IRE1α. By studying mechanisms of the UPR through fasting and feeding contexts, critical information can be formulated about UPR proteins role in bile acid and lipid regulation.
Effect of Fasting and Deoxycholic Acid Feeding in Xbp1-Knockout and Xbp1-Flox Control Mice
B-131 Grainger
The unfolded protein response (UPR) is a protective response which helps the cell adapt to intracellular stressors. Recent data indicates that the UPR affects hepatic lipid and glucose metabolism. This study analyzes how the individual and combined effects of bile acid feeding followed by fasting or non-fasting periods affect phosphorylated inositol requiring enzyme 1 alpha (IRE1α), a UPR protein. Cre+ X-box binding protein 1 (Xbp1) knock-out mice (lacking hepatic Xbp1) and Cre- mice (containing hepatic Xbp1) were either fed chow or 0.3% deoxycholic acid (a bile salt) for three days. After feeding, the mice were either left non-fasted or were fasted for 4 hours before sacrifice. Western blots indicate that phosphorylated- IRE1α is prominent in 4 hours fasted DCA-fed Cre+ mice and 4 hours fasted chow-fed Cre+ mice, which may be due to loss of suppression by XBP1 in knockout mice. Further testing will examine how IRE1α alters with different fasting periods in chow and DCA-fed mice. Additionally, XBP1 will be studied to analyze its interaction with its upstream target, IRE1α. By studying mechanisms of the UPR through fasting and feeding contexts, critical information can be formulated about UPR proteins role in bile acid and lipid regulation.