Figure 5.

Intestine-specific overexpression of LDLR improves glucose metabolism. (A) Real-time PCR was used to validate several targets that we selected based on a microarray study of the duodenum. The targets included Glut1 and several key factors and enzymes of cholesterol metabolism: Ldlr, Npc1l1, and Pcsk9. (B) Heat map and color key for significantly regulated genes related to glucose metabolism in the duodenum. A comparison of transgenic vs wild-type mice is shown. Each cell represents the average log₂ fold change. The list was based on the microarray gene expression analysis of the duodenum. (C) List of the statistically significant metabolic networks in the duodenum. A comparison of transgenic vs wild-type mice is shown. These pathways were determined using Metacore™ (Thompson Reuters). Most of these networks are related to the metabolism of glucose and other carbohydrates, suggesting that LDLR overexpression affects glucose metabolism of the intestine. (D) Chow-fed C57BL/6-TG(Vil-LDLR) mice had lower fasting blood glucose (FBG) levels compared with controls. (E) Fasting blood glucose levels normalized in transgenic mice fed with a HFHC diet. (F) Blood glucose levels were lower at weaning. These measurements were performed without fasting [random blood glucose (RBG) levels]. Statistics: n = 3 to 15 per group; results are expressed as mean ± SD; one-sample t test for real-time PCR, t test for other comparisons between groups. *P < 0.05. TG, C57BL/6-TG(Vil-LDLR) transgenic mice; WT, wild-type littermate controls.