Abstract: SA-PO782
Distinct Glucose vs. Fructose-Specific Gene Regulation in Small Intestine
Session Information
- Hypertension and CVD: Mechanisms
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1503 Hypertension and CVD: Mechanisms
Authors
- Soleimani, Manoocher, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Barone, Sharon L., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Zahedi, Kamyar A., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Argyropoulos, Christos, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
Background
Metabolic syndrome is manifested by visceral obesity, hypertension, and insulin resistance and is highly prevalent in US population. The pathogenesis of hypertension in metabolic syndrome remains speculative. Americans are consuming >300 calories/day of sugar- mostly in the form of fructose and sucrose (a glucose/fructose disaccharide). In addition, Americans are consuming 2-3 times the recommended amount of salt. How the interaction between excessive salt, carbohydrates, and their transporters in the small intestine may lead to salt sensitivity of hypertension in metabolic syndrome remains unknown.
Increased consumption of sucrose (which hydrolyzes to glucose and fructose) increases systemic blood pressure in rodents. There are distinct pathways mediating the absorption of glucose vs. fructose in the small intestine. Glucose is absorbed primarily via SGLT1; whereas, fructose is primarily absorbed via GLUT5.
Methods
Mice were fed a 60% glucose or fructose diet (vs. control) for 2 weeks. RNA seq analysis and expression studies were performed on RNA isolated from mouse jejunum.
Results
RNA seq analysis and northern hybridization on jejuna of experimental animals shows significant activation of the mineralocorticoid receptor (MR) in glucose-, but not fructose-fed mice. Glucocorticoid receptor (GR) expression did not change in glucose- or fructose-fed mice. In addition, the expression of SGK1, which regulates the expression of NHE3 and SGLT1 was increased significantly in glucose-fed, but not fructose-fed mice. The expression of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which inactivates glucocorticoids, is decreased in glucose-fed mice, which ensures that glucocorticoids remain active and can efficiently compete for binding with MR. GLUT5 was increased more significantly in fructose-fed, whereas SGLT1 was increased more significantly in glucose-fed mice.
Conclusion
Our studies demonstrate that increased glucose consumption activates the MR and SGK1, but downregulates 11β-HSD2 in the small intestine. The upregulation of MR and SGK1 can facilitate further salt absorption via NHE3 and SGLT1 working in parallel and stimulated by glucocorticoids. We propose that increased carbohydrate consumption (including sucrose) can stimulate salt absorption in the small intestine by distinct mechanisms.
Funding
- Veterans Affairs Support