CBBM Lecture "LIVER-TO-FAT RETINOL TRANSPORT CONTROLS COLD-MEDIATED ADIPOSE TISSUE BROWNING" by


Assoc.Prof. Priv.Doz. Dr. Florian Kiefer, PhD, Clinical Devision of Endocrinology and Metabolism, University Hospital Department of Internal Medicine III, Medical University Vienna, Austria


will take place on Tuesday, November 12, 2019 from 17:15 to 18:15 hours in CBBM Building, Ground Floor, Seminar Room B1/B2.

Host: Prof. Dr. Sebastian Schmid
Department of Internal Medicine I
University of Lübeck


Abstract

Transformation of white into brown-like fat (“browning”) reduces obesity in many preclinical models and holds great promise as therapeutic concept in metabolic disease. Vitamin A metabolites (retinoids) have been linked to thermogenic programming of adipose tissue (AT), however the physiologic importance of systemic retinoid metabolism for AT browning and adaptive thermogenesis is unknown. Here we show that cold stimulation in mice and humans leads to an increase in circulating retinol and its plasma transporter, retinol binding protein (RBP). Cold exposure shifts retinol abundance from liver towards subcutaneous white AT (sWAT) which correlates with enhanced thermogenic gene expression. Cold-mediated retinoid flux is abrogated in Rbp deficient (Rbp-/-) mice, a model with defective retinoid transport. As a consequence, AT browning and mitochondrial function are dramatically impaired in sWAT, which renders Rbp-/- mice cold intolerant. Rbp deficiency also attenuates cold-induced lipid clearance most likely due to decreased oxidative capacity. In humans, cold-mediated retinol increase is associated with enhanced lipid utilization, and retinol stimulation in primary human adipocytes promotes thermogenic gene expression and mitochondrial respiration. In conclusion, systemic vitamin A abundance is regulated by cold exposure in mice and humans and intact retinoid shuttling is essential for cold-induced AT browning and lipid turnover.


Biosketch

Dr. Kiefer studied medicine in Vienna and Heidelberg and graduated in 2006. He also obtained a PhD degree from the Medical University Vienna in 2010. After a short period in the clinic he joined Harvard Medical School as a Postdoctoral Research fellow where Dr. Kiefer became interested in brown fat physiology and novel molecular pathways of adipose tissue browning and adaptive thermogenesis. After his return to Austria he finished his clinical trainig as an Endocrinologist. Dr. Kiefer is currently serving as an Associate Professor and Head of the Endocrine Outpatient Clinic at the Division of Endocrinolgy & Metabolism at the Medical University of Vienna. He is also a leading a research group focused on brown fat and energy metabolism research. Dr. Kiefer coordinates the Endocrine teaching program at the Medical University of Vienna and he is currently serving as the Secretary of the Austrian Society of Endocrinology and Metabolism.