Seminar Abstract

Seminar date: 16-03-2010

Antonio Moschetta Laboratory of Lipid Metabolism and Cancer, University of Bari, Italy

Several steps of the HDL-mediated reverse cholesterol transport (RCT) are transcriptionally regulated by the nuclear receptors LXRs in the macrophages, liver and intestine. Systemic LXR activation via synthetic ligands induces RCT but also causes increased hepatic fatty acid synthesis and steatosis, limiting the potential therapeutic use of LXR agonists. During the last few years, the participation of the intestine in the control of RCT has become more evident. Using intestinal-specific genetic LXR activation, we fully characterize the molecular and metabolic scenario that leads to decreased intestinal cholesterol absorption, improved lipoprotein profile and increased RCT in vivo in absence of hepatic steatosis. These events protect against atherosclerotic in the background of the LDLR deficient mice. Thus, our study elects the intestine as a key player in the LXR-driven protective environment against cardiovascular disease.