Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany
Ismene Karakasilioti
Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany; Center of Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, Cologne, Germany
Janine Altmüller
Center of Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Cologne Center for Genomics, University of Cologne, Cologne, Germany
Peter Frommolt
Bioinformatics Facility, Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany
Jens Brüning
Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany; Center of Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, Cologne, Germany
Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany
In the arcuate nucleus of the hypothalamus (ARH) satiety signaling (anorexigenic) pro-opiomelanocortin (POMC)-expressing and hunger signaling (orexigenic) agouti-related peptide (AgRP)-expressing neurons are key components of the neuronal circuits that control food intake and energy homeostasis. Here, we assessed whether the catecholamine noradrenalin directly modulates the activity of these neurons in mice. Perforated patch clamp recordings showed that noradrenalin changes the activity of these functionally antagonistic neurons in opposite ways, increasing the activity of the orexigenic NPY/AgRP neurons and decreasing the activity of the anorexigenic POMC neurons. Cell type-specific transcriptomics and pharmacological experiments revealed that the opposing effect on these neurons is mediated by the activation of excitatory α1A - and β- adrenergic receptors in NPY/AgRP neurons, while POMC neurons are inhibited via α2A – adrenergic receptors. Thus, the coordinated differential modulation of the key hypothalamic neurons in control of energy homeostasis assigns noradrenalin an important role to promote feeding.
