Gökhan S. Hotamışlıgil
Gökhan S. Hotamışlıgil, MD, PhD. Is the James S. Simmons Professor of Genetics & Metabolism and Director of the Sabri Ülker Centre for Metabolic Research, Harvard T.H. Chan School of Public Health, Boston, USA. After completing his medical studies at Ankara University, Turkey, Dr. Hotamışlıgil undertook a PhD at Harvard University. His research focuses on the molecular mechanisms of adaptive response systems, especially as they relate to inflammation, metaflammation, and metabolic homeostasis in health and disease. His research group identified the role of the endoplasmic reticulum (ER) as a key locus of metabolic and immunometabolic adaptation, identified key mechanisms that relate to the metabolic functions of the ER, and identified molecules that can target ER, some of which are in clinical trials. In addition, his research has led to the identification of new lipid and peptide hormones that regulate lipid and glucose metabolism and are being developed and tested to treat fatty liver disease and diabetes. Dr. Hotamisligil has been recognized with numerous awards including the Outstanding Scientific Accomplishment Award of the American Diabetes Association, the Wertheimer Award of the International Association of Obesity, Science Award of the Vehbi Koç Foundation, Roy Greep Award for Outstanding Research of the Endocrine Society, and the International Danone Prize. Dr. Hotamışlıgil is a permanent member of the Turkish Academy of Sciences.
Monday 05 October 12:45
Foundations of immunometabolism and implications for metabolic health and disease
The field of immunometabolism encompasses investigation of the regulatory pathways which control interactions between immune and metabolic responses as critical drivers of chronic disease. In the last two decades it has become clear that overlapping and redundant inflammatory pathways play pleiotropic and important roles in metabolism, and that the metabolic state is a critical determinant of immune function. Additionally, components of both the innate and adaptive immune system modulate metabolism. This is highly relevant in the context of the obesity pandemic, as obesity has been shown to drive the production of many abnormal immune mediators, and also modify the regulation of immune response signalling.
Adipocytes have been a key focus of research in this field. Studies have shown that adipocytes produce and regulate many metabolic and hormonal signals, with profound effects on systemic endocrine equilibrium. In the setting of metabolic stress and during obesity, these cells exhibit an inflammatory capacity which is key to the pathogenesis of insulin resistance and diabetes. Molecular mechanisms underlying the link between inflammatory responses and insulin action include obesity-related activation of the serine/threonine kinase, JNK. In addition, other innate immune cell types play key roles in homeostatic and adaptive settings in the adipose tissue. Recently, there has been accumulating evidence that the adaptive immune system may also contribute to insulin sensitivity,
Research has identified a critical role for circulating lipids in modulating insulin resistance. In addition, fatty acid binding proteins are central to many components of the metabolic syndrome, and play a role in modulating inflammation, especially upon exposure to lipids.
While research suggests translational potential, the complexity of networks between immunity and metabolic responses in chronic disease poses practical challenges. Despite this, therapeutic targeting indicated by experimental and genomic studies has shown promise in small clinical studies and suggests novel preventive and treatment approaches to the management of obesity, diabetes and atherosclerosis.
Prentice KJ, Saksi J, Hotamisligil GS. Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses. J Lipid Res 2019;60:734-40.
Bartelt A, Widenmaier SB, Schlein C, Johann K, Goncalves RLS, Eguchi K, Fischer AW, Parlakgül G, Snyder NA, Nguyen TB, Bruns OT, Franke D, Bawendi MG, Lynes MD, Leiria LO, Tseng YH, Inouye KE, Arruda AP, Hotamisligil GS. Brown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity. Nat Med 2018;24:292-303.
Liu L, Inouye KE, Allman WR, Coleman AS, Siddiqui S, Hotamisligil GS, Akkoyunlu M. TACI-Deficient macrophages protect mice against metaflammation and obesity-induced dysregulation of glucose homeostasis. Diabetes 2018;67:1589-603.