TY - JOUR
T1 - Improved metabolic control by depletion of Liver X Receptors in mice
AU - Schuster, Gertrud U.
AU - Johansson, Lisen
AU - Kietz, Silke
AU - Stulnig, Thomas M.
AU - Parini, Paolo
AU - Gustafsson, Jan Åke
N1 - Funding Information:
We thank Prof. Bo Angelin for critically reading the manuscript. This study was supported by the Swedish Science Council, by the Thuring, the Tore Nilsson, the Ruth and Bertil Julin, the Åke Wiberg, and the Söderberg Foundations, by the Swedish Society of Medicine and the Swedish Heart–Lung-Foundation, by the Swedish Cancer Society, the Austrian Science Fund (P18776 to T.M.S.) and the Skoda Research Award of the Austrian Society for Internal Medicine, and by KaroBio AB, Sweden.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/9/15
Y1 - 2006/9/15
N2 - 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 LXRα-/-β-/- mice. Irrespective of diets, LXRα-/-β-/- 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 LXRα-/-β-/- mice and increased hepatic triglyceride content and mRNA levels of lipogenic genes in wild-type and LXRα-/-β-/- mice, proportionally. In wild-type mice high carbohydrate diet was associated with induced expression of LXR (1.5-fold), despite unchanged SREBP-1c expression. LXRα-/-β-/- mice responded to this diet by induction of SREBP-1c. Our study suggests that in LXRα-/-β-/- mice, glucose utilization seems to be privileged possibly due to reduced circulating free fatty acid levels.
AB - 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 LXRα-/-β-/- mice. Irrespective of diets, LXRα-/-β-/- 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 LXRα-/-β-/- mice and increased hepatic triglyceride content and mRNA levels of lipogenic genes in wild-type and LXRα-/-β-/- mice, proportionally. In wild-type mice high carbohydrate diet was associated with induced expression of LXR (1.5-fold), despite unchanged SREBP-1c expression. LXRα-/-β-/- mice responded to this diet by induction of SREBP-1c. Our study suggests that in LXRα-/-β-/- mice, glucose utilization seems to be privileged possibly due to reduced circulating free fatty acid levels.
KW - Insulin receptor substrate 2
KW - Liver X Receptor
KW - Serum glucose levels
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U2 - 10.1016/j.bbrc.2006.07.044
DO - 10.1016/j.bbrc.2006.07.044
M3 - Article
C2 - 16876124
AN - SCOPUS:33746843565
VL - 348
SP - 176
EP - 182
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -