Energy imbalance alters Ca2+ handling and excitability of POMC neurons

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.

Keywords: POMC-neuron; calcium; calcium handling; hypothalamus; mouse; neuroscience; obesity.