Energy imbalance alters Ca2+ handling and excitability of POMC neurons

نویسندگان

  • Lars Paeger
  • Andreas Pippow
  • Simon Hess
  • Moritz Paehler
  • Andreas C Klein
  • Andreas Husch
  • Christophe Pouzat
  • Jens C Brüning
  • Peter Kloppenburg
چکیده

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.

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2017