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Updated: Aug 6, 2026
Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes
Published on: September 9, 2021
Improved metabolic control by depletion of Liver X Receptors in mice
Gertrud U Schuster1, Lisen Johansson, Silke Kietz
1Department of Biosciences and Nutrition, Karolinska University Hospital, Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden. gschuster@ucdavis.edu
Abstract:
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.
Insights
Liver X Receptors (LXRs) are key regulators of metabolism. LXR-deficient mice show altered glucose and fatty acid levels, suggesting a potential role in metabolic disease management.
Area of Science:
- Metabolic regulation
- Endocrinology
- Molecular biology
Background:
- Liver X Receptors (LXRs) are crucial for lipid and carbohydrate metabolism and insulin signaling.
- LXR ligands have shown potential as anti-diabetic agents by lowering plasma glucose in hyperglycemic rodents.
Purpose of the Study:
- To investigate the metabolic effects of a high-carbohydrate diet in mice lacking both LXRalpha and LXRbeta (LXRalpha(-/-)beta(-/-)).
- To understand the role of LXRs in glucose homeostasis and lipogenesis under dietary challenges.
Main Methods:
- Comparative analysis of LXRalpha(-/-)beta(-/-) mice and wild-type controls fed standard and high-carbohydrate diets.
- Measurement of plasma glucose, insulin, C-peptide, and free fatty acid levels.
- Assessment of hepatic triglyceride content and lipogenic gene expression (e.g., SREBP-1c).
Main Results:
- LXRalpha(-/-)beta(-/-) mice exhibited lower basal plasma levels of fatty acids, insulin, and C-peptide compared to wild-type mice.
- A high-carbohydrate diet reduced plasma glucose and HOMA-index in LXRalpha(-/-)beta(-/-) mice.
- Hepatic triglyceride content and lipogenic gene expression increased in both genotypes on a high-carbohydrate diet, with LXRalpha(-/-)beta(-/-) mice showing SREBP-1c induction.
Conclusions:
- Glucose utilization appears to be enhanced in LXRalpha(-/-)beta(-/-) mice, potentially due to reduced circulating free fatty acids.
- These findings highlight a complex interplay between LXRs, diet, and metabolic regulation, offering insights into potential therapeutic strategies for metabolic disorders.
