Dear All: 

Institute of Molecular Medicine
Center for Life Sciences
Research Seminar

 

Title：Lipid storage and trafficking in human metabolic and neurodegenerative disorders

Speaker：Hongyuan Yang, Ph.D.

                Professor and NHMRC Senior Research Fellow

              School of Biotechnology and Biomolecular Sciences

              The University of New South Wales, Australia

Time：2015年12月7日（星期一）下午2:00-3:00

Place：北京大学生命科学学院邓祐才报告厅

Host：北京大学分子医学研究所        陈晓伟(Tel. 6276-8919)

Abstract: Obesity is characterized by accumulation of adipocytes loaded with lipid droplets (LDs). We have recently identified a number of yeast gene products that regulate the size and number of LDs. Notably, deletion of a previously uncharacterized gene, FLD1, results in the formation of “super-sized”LDs. The human orthologue of Fld1p is SEIPIN, and loss-of-function mutations of the SEIPIN gene are associated with human Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2). We use mouse and fly models to confirm an essential role of SEIPIN in adipogenesis. Therefore, SEIPIN regulates both systemic (adipocyte differentiation) and cellular (LD formation) lipid storage. Our recent results suggest that SEIPIN functions in the metabolism of phospholipids, and that SEIPIN deficiency causes accumulation of certain lipid species, such as phosphatidic acid. These accumulated lipids may interfere with PPARgamma function during adipocyte differentiation in preadipocytes, and may also cause morphological changes of LDs in other cell types.

Sterols as essential components of eukaryotic membranes must be sorted precisely and transported efficiently. Abnormal subcellular distribution of cholesterol is associated with heart and neurodegenerative diseases including Alzheimer’s disease and Niemann Pick C disease, which is characterized by cholesterol accumulation in endosomes and lysosomes. The intracellular trafficking of cholesterol remains a challenging subject in cell biology. We have recently identified novel cytosolic proteins essential for cholesterol efflux from late endosomes and lysosomes, including ORP5, Hrs/Vps27 and Vps4.