Sander Kersten
Sander Kersten
Division Director; Schleifer Family Professor in the College of Human Ecology Division of Nutritional Sciences
Division of Nutritional Sciences
Office

127 Savage Hall

Biography

Sander Kersten, Ph.D. is the director of the Division of Nutritional Sciences and the Schleifer Family Professor at Cornell University.  Dr. Kersten received his MSc degree in Human Nutrition from Wageningen University in 1993, and his Ph.D. degree in Nutritional Biochemistry from Cornell University in 1997. After a postdoctoral stay in the laboratory of Dr. Walter Wahli at the University of Lausanne, Switzerland, he moved back to Wageningen University in 2000 with a career development grant from the Royal Netherlands Academy of Arts and Sciences. He was appointed to Associate Professor in 2006 and Full Professor in 2011. In 2014 he became Chair of the Nutrition, Metabolism and Genomics group and in 2019 Chairman of the Division of Human Nutrition and Health at Wageningen University. He will join Cornell in January 2024.

Research in his group aims to elucidate the molecular mechanism that underlies the regulation of lipid metabolism in the liver and adipose tissue during fasting and feeding. In the past, his group demonstrated the importance of the transcription factor PPARα in the metabolic response to fasting in the liver. Using various human liver model systems in combination with transcriptomics, his work also revealed the importance of PPARα in gene regulation and nutrient metabolism in the human liver. In addition, his team elucidated the mechanism responsible for the regulation of fat uptake into adipose tissue during fasting. Specifically, his group discovered the protein ANGPTL4 and elucidated its role as a crucial regulator of lipid uptake into adipose tissue by interfering with the function of lipoprotein lipase. His current research is concentrated on identifying the role of several novel fasting-regulated genes in lipid metabolism in adipose tissue and the liver.

Research interests

Throughout human evolution, the greatest threat to the survival of our ancestors was the recurrent periods of undernutrition and fasting. Consequently, fasting has been a key selective pressure shaping nutrient and energy metabolism. The intricate mechanisms directing lipid and energy metabolism during starvation allowed our ancestors to survive long periods without food. In the modern world of caloric excess, however, these same mechanisms contribute to the unprecedented growth in obesity and related diseases. In my view, the development of obesity and related metabolic disturbances can only be fully understood by having detailed insight into how lipid and energy metabolism respond to fasting and how this metabolic response is regulated. Accordingly, further mechanistic understanding of how humans respond to fasting could hold the key to the design of effective preventive and therapeutic strategies for overnutrition and its pathological sequelae, including obesity, insulin resistance, non-alcoholic fatty liver disease, and atherosclerosis.

The common thread throughout my professional career has been the study of the mechanisms and functional impact of gene regulation by lipids during feeding and fasting. The main aim of my research is to better understand how lipid metabolism is regulated during feeding and fasting and how lipids govern specific functional outcomes and orchestrate their own metabolism. The primary focus is on the key organs relevant to lipid metabolism represented by the liver and adipose tissue, the transport of lipids to these organs, and the interplay between these organs and other relevant systems such as the immune system. In my research, a multi-pronged approach is used that ranges from dietary intervention studies in human subjects to physiological experiments in transgenic animals and detailed mechanistic studies in vitro.

Keywords: fasting, fatty acids, lipid/lipoprotein metabolism, liver, adipose tissue, macrophages, NAFLD, atherosclerosis, diabetes, obesity, Peroxisome Proliferator-Activated Receptors, lipoprotein lipase, Angiopoietin-like proteins

Ruppert PMM, Kersten S. (2023) Mechanisms of hepatic fatty acid oxidation and ketogenesis. Trends in Endocrinology and Metabolism. Nov 6:S1043-2760(23)00215-1. doi: 10.1016/j.tem.2023.10.002.

Kersten S. (2023) ANGPTL4/8 promotes plasmin-mediated cleavage of LPL inhibitors.  J Lipid Res. 64:100438. doi: 10.1016/j.jlr.2023.100438.

Deng L, Kersten S, Stienstra S. (2023) Triacylglycerol uptake and handling by macrophages: from fatty acids to lipoproteins. Prog. Lipid Res. 92:101250. doi: 10.1016/j.plipres.2023.101250.

Deng L, Wu SA, Qi L, Kersten S. (2023) HILPDA is a lipotoxic marker in adipocytes that mediates the autocrine negative feedback regulation of triglyceride hydrolysis by fatty acids and alleviates cellular lipotoxic stress. Mol Metab. 75:101773.

Abdon B, Liang Y, da Luz Scheffer D, Torres M, Shrestha N, Reinert RB, Lu Y, Pederson B, Bugarin-Lapuz A, Kersten S, Qi L. (2023) Myocyte-specific SEL1L-HRD1 ER-associated degradation is indispensable for maintaining postnatal muscle hypertrophy and systemic energy metabolism in mice. JCI Insights. 8:e170387. doi: 10.1172/jci.insight.170387.

Kersten S. (2023) The impact of fasting on adipose tissue metabolism. Biochim Biophys Acta Mol Cell Biol Lipids. 1868:159262. doi: 10.1016/j.bbalip.2022.159262.

Landfors F, Chorell E, Kersten S. (2023) Genetic mimicry analysis reveals the specific lipases targeted by the ANGPTL3/ANGPTL8 complex and ANGPTL4. J Lipid Res. 64: 100313. doi: 10.1016/j.jlr.2022.100313.

1993, M.Sc, Human Nutrition, Wageningen University

1997, Ph.D., Nutritional Biochemistry, Cornell University

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