POMC neuronal heterogeneity in energy balance and beyond: an integrated view
Nat Metab. 2021-02-25; :
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Quarta C(1), Claret M(2)(3), Zeltser LM(4)(5), Williams KW(6), Yeo GSH(7), Tschöp MH(8)(9), Diano S(10)(11), Brüning JC(12)(13)(14)(15)(16), Cota D(17).
(1)University of Bordeaux, Neurocentre Magendie, Physiopathologie de la
Plasticité Neuronale, INSERM U1215, Bordeaux, France.
(2)Neuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d’Investigacions
Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
(3)Centro de Investigación Biomédica en Red (CIBER), Diabetes y Enfermedades
Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
(4)Naomi Berrie Diabetes Center, Columbia University, New York, NY, USA.
(5)Department of Pathology and Cell Biology, Columbia University, New York, NY,
(6)Center for Hypothalamic Research, Department of Internal Medicine, University
of Texas Southwestern Medical Center, Dallas, TX, USA.
(7)MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research
Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s
Hospital, Cambridge, UK.
(8)Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz
Zentrum München, German Research Center for Environmental Health, Neuherberg,
(9)Division of Metabolic Diseases, Department of Medicine, Technische
Universität, Munich, Germany.
(10)Institute of Human Nutrition, Columbia University Irving Medical Center, New
York, NY, USA.
(11)Department of Molecular Pharmacology and Therapeutics, Columbia University
Irving Medical Center, New York, NY, USA.
(12)Department of Neuronal Control of Metabolism, Max Planck Institute for
Metabolism Research, Cologne, Germany.
(13)Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University
Hospital Cologne, Cologne, Germany.
(14)Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases
(CECAD), University of Cologne, Cologne, Germany.
(15)Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne,
(16)National Center for Diabetes Research (DZD), Neuherberg, Germany.
(17)University of Bordeaux, Neurocentre Magendie, Physiopathologie de la
Plasticité Neuronale, INSERM U1215, Bordeaux, France. .
Hypothalamic AgRP and POMC neurons are conventionally viewed as the yin and yang
of the body’s energy status, since they act in an opposite manner to modulate
appetite and systemic energy metabolism. However, although AgRP neurons’
functions are comparatively well understood, a unifying theory of how POMC
neuronal cells operate has remained elusive, probably due to their high level of
heterogeneity, which suggests that their physiological roles might be more
complex than initially thought. In this Perspective, we propose a conceptual
framework that integrates POMC neuronal heterogeneity with appetite regulation,
whole-body metabolic physiology and the development of obesity. We highlight
emerging evidence indicating that POMC neurons respond to distinct combinations
of interoceptive signals and food-related cues to fine-tune divergent metabolic
pathways and behaviours necessary for survival. The new framework we propose
reflects the high degree of developmental plasticity of this neuronal population
and may enable progress towards understanding of both the aetiology and treatment
of metabolic disorders.