Lipid synthesis and storage in human metabolic disorders

Lipid synthesis and storage in human metabolic disorders

Lipid synthesis and storage in human metabolic disorders (#20)

H. Robert Yang ¹

School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia

Obesity is characterized by accumulation of adipocytes loaded with lipid droplets (LDs). By genetic screening in yeast, we identified a large number of gene products that regulate the size and number of LDs. In particular, we demonstrate that deletion of a previously uncharacterized gene, FLD1, results in the formation of “super-sized” LDs (>50 times the volume of normal ones). Interestingly, null mutations of SEIPIN (the human orthologue of Fld1p) 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 two important aspects of lipid storage: adipocyte differentiation (systemic lipid storage) and lipid droplet formation (cellular 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, causing severe lipodystrophy. These lipid species may also cause morphological changes of LDs, e.g. the formation of “supersized” LDs, in other cell types. These findings may lead to novel therapeutic strategies against human congenital generalized lipodystrophies.

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Yang, H

Professor Hongyuan Robert Yang obtained his Bachelor of Medicine degree from Peking University (Beijing, China) in 1993; and his Ph.D. from Columbia University (New York, USA) in 1998. Soon after, he started his own laboratory as a lecturer at the Department of Biochemistry, National University of Singapore where he was promoted to associate professor with tenure. He joined the University of New South Wales (Sydney, Australia) as a senior lecturer in 2007, and became a professor at the end of 2012. He was an Australian Research Council Future Fellow from 2010 to 2013, and he is currently a Senior Research Fellow of the National Health and Medical Research Council, Australia. He recently joined the University of Texas Health Science Center, Houston, USA. His work focuses on lipid storage and trafficking in eukaryotic cells and animals. He has published over 70 peer-reviewed articles and book chapters. His group identified a number of gene products that regulate the growth of lipid droplets. One of those, SEIPIN, is also essential for adipogenesis. His group characterized SEIPIN using a number of model systems including yeast and mice, and discovered a role for SEIPIN in phospholipid metabolism. These findings may lead to novel therapeutic strategies against obesity and congenital generalized lipodystrophy. His group also identified and characterized a number of proteins that regulate cellular cholesterol trafficking and homeostasis.

Lipid synthesis and storage in human metabolic disorders (#20)

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