Can manipulating liver X receptors (LXRs) unlock new avenues for metabolic control? This paper explores the physiological role of LXRs, revealing their influence on lipogenesis, the process of fatty acid biosynthesis. Through the administration of synthetic LXR agonists like T0901317 to mice and hamsters, the study demonstrates that LXR activation leads to increased expression of key fatty acid biosynthetic genes. The research uncovers that LXRs mediate an increase in plasma triglyceride and phospholipid levels, suggesting a direct link between LXR activation and lipid metabolism. Further investigations in cell cultures and animal models indicate that this increase in plasma lipids occurs through LXR-mediated induction of the sterol regulatory element-binding protein 1 (SREBP-1) lipogenic program. This program is essential for plasma lipids level increment. This study reveals that LXR plays a vital part in the process of cholesterol and lipid regulation. These findings open new avenues for therapeutic interventions targeting metabolic disorders, including dyslipidemia and related cardiovascular conditions. The discovery and application of synthetic LXR ligands may help in the regulation of the expression of major fatty acid biosynthetic genes.
Published in Genes & Development, this research aligns with the journal's focus on gene regulation and its impact on development and physiological processes. By elucidating the role of LXRs in controlling lipogenesis through SREBP-1, the study directly contributes to the understanding of how gene expression influences metabolic pathways. This paper provides a mechanism for sterol regulation which is relevant for the journal.