Stress and metabolic functions

Maintenance of energy homeostasis in the presence of real or perceived challenges requires numerous adaptive responses involving changes in the central nervous and neuroendocrine systems. Energy homeostasis is ultimately governed by the brain, where a variety of afferent signals reflect the animal’s nutritional state and its external environment. These signals, which may consist of physiological and/or psychological stressful stimuli, are integrated in order to modulate efferent pathways that control feeding behavior and energy expenditure. The goal of recent and ongoing projects in the lab determine the physiological role of central type 1 and type 2 corticotropin releasing factor (CRF) receptors, expressed in discrete brain nuclei, in mediating feeding behavior and energy homeostasis under normal and stressful conditions. We are using integrated molecular, biochemical, physiological and behavioral methods, with focus on the generation of mutant mice models as an in vivo tool, to study the physiological roles of CRF receptors in coordinating feeding behavior and energy homeostasis under normal and stressful conditions. Specifying the contributions of the CRF family of ligands and receptors to the maintenance of homeostasis and to stress-linked allostasis may improve our ability to design therapeutic interventions and thus manage metabolic and related behavioral disorders.

Relevant Publications

Kuperman, Y., Weiss, M., Dine, J., Staikin, K., Golani, O., Ramot, A., Nahum, T., Kuhne, C., Shemesh, Y., Wurst, W., Harmelin, A., Deussing, J.M., Eder, M., Chen A (2016). Crfr1 in Agrp Neurons Modulates Sympathetic Nervous System Activity to Adapt to Cold Stress and Fasting.  Cell Metab. 23: (6):1185-1199.
Greenman Y, Kuperman Y, Drori Y, Asa Sl, Navon I, Forkosh O, Gil S, Stern N, Chen A, (2013). Postnatal Ablation of Pomc Neurons Induces an Obese Phenotype Characterized by Decreased Food Intake and Enhanced Anxiety-Like Behavior.  Molecular Endocrinology. 27: (7):1091-1102.
Rousso-Noori L, Knobler H, Levy-Apter E, Kuperman Y, Neufeld-Cohen A, Keshet Y, Akepati Vr, Klinghoffer Ra, Chen A, Elson A, (2011). Protein Tyrosine Phosphatase Epsilon Affects Body Weight by Downregulating Leptin Signaling in a Phosphorylation-Dependent Manner.  Cell Metabolism. 13: (5):562-572.
Kuperman Y, Issler O, Regev L, Musseri I, Navon I, Neufeld-Cohen A, Gil S, Chen A, (2010). Perifornical Urocortin-3 Mediates the Link Between Stress-Induced Anxiety and Energy Homeostasis.  Proceedings of the National Academy of Sciences of the United States of America. 107: (18):8393-8398.
Kuperman Y, Issler O, Vaughan J, Bilezikjian L, Vale W, Chen A, (2011). Expression and Regulation of Corticotropin-Releasing Factor Receptor Type 2 Beta in Developing and Mature Mouse Skeletal Muscle.  Molecular Endocrinology. 25: (1):157-169.