Paeger, Lars ORCID: 0000-0001-8716-3483, Pippow, Andreas, Hess, Simon, Paehler, Moritz, Klein, Andreas C., Husch, Andreas, Pouzat, Christophe ORCID: 0000-0002-2844-8099, Bruening, Jens C. and Kloppenburg, Peter (2017). Energy imbalance alters Ca2+ handling and excitability of POMC neurons. eLife, 6. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Paeger, LarsUNSPECIFIEDorcid.org/0000-0001-8716-3483UNSPECIFIED
Pippow, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paehler, MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, Andreas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Husch, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pouzat, ChristopheUNSPECIFIEDorcid.org/0000-0002-2844-8099UNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kloppenburg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-223409
DOI: 10.7554/eLife.25641
Journal or Publication Title: eLife
Volume: 6
Date: 2017
Publisher: ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication: CAMBRIDGE
ISSN: 2050-084X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACTIVATED POTASSIUM CHANNELS; SPIKE-FREQUENCY ADAPTATION; ENDOPLASMIC-RETICULUM STRESS; LEPTIN RESISTANCE; SMALL-CONDUCTANCE; K+ CHANNELS; INTERMEDIATE-CONDUCTANCE; HYPOTHALAMIC NEURONS; GLUCOSE-HOMEOSTASIS; OBESITY EPIDEMICMultiple languages
BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22340

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