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Lactate activates hypothalamic POMC neurons by intercellular signaling
P Órdenes1, P S Villar2, E Tarifeño-Saldivia3
1Laboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.
Scientific Reports
|November 5, 2021
Summary
Lactate signals to hypothalamic POMC neurons through astrocyte-neuron communication, not directly. The lactate receptor (HCAR1) is found in astrocytes, influencing POMC neuron activity.
Area of Science:
- Neuroscience
- Metabolism
- Cellular Signaling
Background:
- Hypothalamic POMC neurons regulate energy balance.
- Glucose regulates POMC neurons intracellularly.
- Lactate's role as a signaling molecule in POMC neuron regulation is unclear.
Purpose of the Study:
- Investigate lactate's effect on POMC neurons.
- Determine the location and function of the lactate receptor, hydroxycarboxylic acid receptor 1 (HCAR1).
- Elucidate the mechanism of lactate-mediated POMC neuron regulation.
Main Methods:
- Conditional genetic labeling of POMC neurons.
- Patch-clamp recordings to assess neuronal excitability.
- Pharmacological manipulation using HCAR1 agonist (3Cl-HBA), pertussis toxin (PTX), and lactate transporter blocker (4-CIN).
- Immunohistochemistry to determine HCAR1 localization.
Main Results:
- L-Lactate and HCAR1 agonist (3Cl-HBA) depolarized POMC neurons.
- Depolarization was sensitive to pertussis toxin (PTX), indicating Gαi/o-protein-coupled receptor involvement.
- A subset of POMC neurons showed lactate-induced depolarization sensitive to the lactate transporter blocker 4-CIN, suggesting intracellular mechanisms.
- HCAR1 was localized to astrocytes, not POMC neurons.
Conclusions:
- Lactate influences POMC neuron activity.
- HCAR1 is not expressed in POMC neurons but is present in astrocytes.
- A novel astrocyte-neuron communication pathway mediates lactate's effects on POMC neurons.
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