Abstract: The present invention relates to methods for elevating high density lipoprotein (HDL) plasma levels, decreasing the absorption of dietary cholesterol in the intestine, decreasing the plasma level of low density lipoprotein (LDL), and increasing the conversion of cholesterol to bile acids, utilizing LXR? selective agonists, usually without elevating the plasma levels of triglycerides. Also provided are methods of using such agonists to treat metabolic diseases alone or in combination with other active agents. Also provided are methods for decreasing hyperglycemia and insulin resistance methods for treating type II diabetes, and methods for treating type II diabetes and reducing the cardiovascular complications of type II diabetes, utilizing an LXR agonist. Further provided are methods for treating obesity and methods for treating the complications of obesity including type II diabetes, cardiovascular disease, hyperlipidemia, and hypertension, administering an LXR?-selective antagonist.

Abstract: The present invention relates to methods for elevating high density lipoprotein (HDL) plasma levels, decreasing the absorption of dietary cholesterol in the intestine, decreasing the plasma level of low density lipoprotein (LDL), and increasing the conversion of cholesterol to bile acids, utilizing LXR&bgr; selective agonists, usually without elevating the plasma levels of triglycerides. Also provided are methods of using such agonists to treat metabolic diseases alone or in combination with other active agents. Also provided are methods for decreasing hyperglycemia and insulin resistance methods for treating type II diabetes, and methods for treating type II diabetes and reducing the cardiovascular complications of type II diabetes, utilizing an LXR agonist. Further provided are methods for treating obesity and methods for treating the complications of obesity including type II diabetes, cardiovascular disease, hyperlipidemia, and hypertension, administering an LXR&agr;-selective antagonist.

Abstract: The retinoid X receptor (RXR) participates in a wide array of hormonal signaling pathways either as a homodimer or as a heterodimer with other members of the steroid/thyroid hormone superfamily of receptors. In accordance with the present invention, the ligand-dependent transactivation function of RXR has been characterized and the ability of RXR to interact with components of the basal transcription machinery has been examined. In vivo and in vitro experiments indicate the RXR ligand binding domain makes a direct, specific and ligand-dependent contact with a highly conserved region of the TATA binding protein (TBP). The ability of mutations that reduce ligand-dependent transcription by RXR to disrupt the RXR-TBP interaction in vivo and in vitro suggests that RXR makes direct contact with the basal transcription machinery in order to achieve activation.