Kersten Lab

My research focuses on uncovering the molecular mechanisms that regulate lipid metabolism in the liver and adipose tissue during fasting and feeding, with particular emphasis on proteins that influence lipid metabolic pathways.

Throughout human evolution, periods of starvation or fasting posed significant survival challenges. As a result, fasting became a major evolutionary force shaping the core mechanisms of nutrient and energy metabolism in humans and other species. In response to fasting, the body activates a coordinated, multi-organ adaptation designed to preserve physiological balance and supply energy to vital tissues when external energy sources are unavailable. This adaptive process is governed by a complex network of transcriptional, translational, and post-translational regulatory systems that have been conserved through evolution to maximize survival during times of nutrient scarcity.

As overnutrition has overtaken undernutrition as the leading global health threat, the once-adaptive "thrifty" metabolic system that helped humans endure periods of fasting now plays a central role in the escalating rates of obesity and related diseases. My research is grounded in the belief that fully understanding the consequences of overnutrition requires a deep exploration of the core mechanisms that regulate lipid and energy metabolism during states of undernutrition and fasting. Gaining deeper mechanistic insight into the human fasting response could be key to developing effective strategies for preventing and treating overnutrition and its associated disorders, such as obesity, insulin resistance, metabolic dysfunction-associated steatotic liver disease (MASLD), and atherosclerosis. Supporting this perspective, many widely pursued therapeutic targets for cardiometabolic diseases are in fact molecules that respond to fasting signals.

A consistent focus throughout my professional career has been exploring how lipids regulate gene expression and the functional consequences of this regulation during feeding and fasting. My research aims to uncover how lipid metabolism is controlled under these nutritional states and how lipids not only drive specific biological functions but also regulate their own metabolic pathways. The primary focus is on the metabolism of lipids in the liver and adipose tissue, the transport of lipids from and to these organs, and the interplay between these organs and other relevant systems, such as the immune system. To investigate these processes, I employ a multi-faceted approach that spans dietary intervention studies in humans, physiological experiments in transgenic animal models, and detailed mechanistic analyses in vitro.

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