Improved metabolic control by depletion of Liver X Receptors in mice.
Liver X Receptors (LXRs) coordinate the regulation of lipid and carbohydrate metabolism and insulin signaling. LXR-ligands lower plasma glucose in hyperglycemic rodents and have consequently been proposed as anti-diabetic agents. We investigated the metabolic effects induced by high carbohydrate diet in LXRalpha(-/-)beta(-/-) mice. Irrespective of diets, LXRalpha(-/-)beta(-/-) mice had reduced fatty acid, insulin, and C-peptide plasma levels than wild-type controls, suggesting a lower insulin production. High carbohydrate diet decreased the plasma glucose levels and the homeostasis model assessment (HOMA)-index in LXRalpha(-/-)beta(-/-) mice and increased hepatic triglyceride content and mRNA levels of lipogenic genes in wild-type and LXRalpha(-/-)beta(-/-) mice, proportionally. In wild-type mice high carbohydrate diet was associated with induced expression of LXR (1.5-fold), despite unchanged SREBP-1c expression. LXRalpha(-/-)beta(-/-) mice responded to this diet by induction of SREBP-1c. Our study suggests that in LXRalpha(-/-)beta(-/-) mice, glucose utilization seems to be privileged possibly due to reduced circulating free fatty acid levels.
Schuster
Gertrud U
GU
Department of Biosciences and Nutrition, Karolinska University Hospital, Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden. gschuster@ucdavis.edu
Johansson
Lisen
L
Kietz
Silke
S
Stulnig
Thomas M
TM
Parini
Paolo
P
Gustafsson
Jan-Ake
JA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004032:Diet; D017353:Gene Deletion; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; D004268:DNA-Binding Proteins; D007328:Insulin; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear