Energy imbalance alters Ca(2+) handling and excitability of POMC neurons

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 Ca(2+) signaling, we investigated whether obesity alters Ca(2+) handling of these neurons in mice. In diet-induced obesity, cellular Ca(2+) handling properties including mitochondrial Ca(2+) uptake capacity are impaired, and an increased resting level of free intracellular Ca(2+) is accompanied by a marked decrease in neuronal excitability. Experimentally increasing or decreasing intracellular Ca(2+) concentrations reproduced electrophysiological properties observed in diet-induced obesity. Taken together, we provide the first direct evidence for a diet-dependent deterioration of Ca(2+) homeostasis in POMC neurons during obesity development resulting in impaired function of these critical energy homeostasis-regulating neurons. DOI: http://dx.doi.org/10.7554/eLife.25641.001