Jon Long

Energy metabolism encompasses the fundamental homeostatic processes by which we regulate our energy storage and energy expenditure. Energy metabolism is highly dynamic and changes according to availability of nutrients, physical activity, or environmental conditions. Dysregulation of energy metabolism is a hallmark of many age-associated chronic diseases, including obesity, type 2 diabetes, dyslipidemias, neurodegeneration, and cancer. Therefore a complete understanding of the molecular pathways of energy metabolism represents an important basic scientific goal with implications for many of the most pressing biomedical problems of our generation. Metabolic tissues including adipose, liver, and muscle play critical roles in energy homeostasis. We are interested in understanding the dynamic endocrine signals that control metabolic tissue function. What are the identities of these signals? How do their levels change in response to physiologic energy stressors? Where are they made? What cell types or tissues do they act on? To answer these questions, we use chemical and mass spectrometry-based technologies as discovery tools. We combine these tools with classical biochemical and genetic techniques in cellular and animal models. Our goal is to discover new molecules and signaling pathways that regulate organismal energy metabolism. Recent studies from our laboratory have identified a family of cold-regulated lipid hormones that stimulate mitochondrial respiration as well as a thermogenic polypeptide hormone regulated by exercise. We suspect that many more remain to be discovered. We anticipate that our approach will uncover fundamental homeostatic mechanisms that control mammalian energy metabolism. In the long term, we hope to translate our discoveries into therapeutic opportunities that matter for metabolic and other age-associated chronic diseases.