Mechanisms driving lipid droplet biogenesis during adipocyte differentiation

The storage of fat within lipid droplets of adipocytes is critical for whole body metabolic health. Here, I will discuss how different mechanisms of fat biosynthesis drive lipid droplet biogenesis in adipocytes. The talk will focus on how differentiating adipocytes remodel the function of their cellular organelles to achieve this important physiological function. In particular, I will highlight the importance of the anabolic function of mitochondria in the provision of substrates for de novo fatty acid synthesis. I will contrast this to classical pathways that take up dietary fatty acids and close on important differences between mouse and human adipocyte metabolism, which might have direct implications for mechanism-based interference with fatty acid liver disease, type-2 diabetes, and obesity.

SPEAKER BIOGRAPHY

Robin’s main research interest is focused on the molecular basis of lipid metabolism in professional fat storing cells called adipocytes.

He carried out his PhD work at the Max Planck Institute of Molecular Cell Biology and Genetics in the lab of Kai Simons. Robin worked on the sorting principles of lipids in the secretory pathway and developed novel organelle isolation methods allowing the rapid purification of several organelles for analysis by mass spectrometry-based proteomics and lipidomics. He presented the first quantitative membrane lipidomes of eukaryotic organelles and identified the role of sphingolipids and sterols in the formation of secretory vesicles at the trans-Golgi network.

During his postdoctoral work at the Harvard Medical School in the lab of Tom Rapoport, Robin reconstituted homotypic ER fusion pathways with purified GTPases of the dynamin family called Atlastin in metazoans and Sey1p in yeast. Depletion of these ER fusogens had unexpected consequences for lipid droplet biology and whole-body lipid metabolism.

Starting his independent work as a group leader at the University of Zurich, Robin switched his focus to lipid droplet biology in adipocytes. The Klemm lab has identified new molecular machinery coupling mitochondria to the ER and adipocyte lipid droplets. The spatial organization of metabolism across several organelles is a fascinating aspect of cellular biochemistry and its regulation and control is absolutely crucial for whole body health and metabolic homeostasis.

In 2020, Robin moved his lab to the University of Oxford. At the Department of Physiology, Anatomy and Genetics, his group investigates the molecular basis of adipocyte LD formation, spatial organization of lipid metabolism and the role of de novo lipogenesis in the etiology of obesity and type II diabetes.