Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
Andreas Pippow
Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
Simon Hess
Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
Moritz Paehler
Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
Andreas C Klein
Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
Andreas Husch
Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
MAP5 - Mathématiques Appliquées à Paris 5, CNRS UMR 8145, Paris, France
Jens C Brüning
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany; Department of Mouse Genetics and Metabolism, Institute for Genetics, Center of Molecular Medicine Cologne, Center for Endocrinology, Diabetes and Preventive Medicine, University Hospital of Cologne, Cologne, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany
Biocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
Satiety-signaling, pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus play a pivotal role in the regulation of energy homeostasis. Recent studies reported altered mitochondrial dynamics and decreased mitochondria- endoplasmic reticulum contacts in POMC neurons during diet-induced obesity. Since mitochondria play a crucial role in Ca2+ signaling, we investigated whether obesity alters Ca2+ handling of these neurons in mice. In diet-induced obesity, cellular Ca2+ handling properties including mitochondrial Ca2+ uptake capacity are impaired, and an increased resting level of free intracellular Ca2+ is accompanied by a marked decrease in neuronal excitability. Experimentally increasing or decreasing intracellular Ca2+ concentrations reproduced electrophysiological properties observed in diet-induced obesity. Taken together, we provide the first direct evidence for a diet-dependent deterioration of Ca2+ homeostasis in POMC neurons during obesity development resulting in impaired function of these critical energy homeostasis-regulating neurons.
