Hypothalamic POMC neurons promote cannabinoid-induced feeding

Area of Science:

• Neuroscience
• Endocrinology
• Molecular Biology

Background:

• Hypothalamic pro-opiomelanocortin (POMC) neurons are traditionally known to promote satiety.
• Cannabinoid receptor 1 (CB1R) plays a critical role in the central regulation of food intake.

Purpose of the Study:

• To investigate the role of POMC neurons in CB1R-controlled feeding in sated mice.
• To determine if CB1R activation affects POMC neuron activity and its impact on feeding behavior.

Main Methods:

• Utilized chemical agonists to promote CB1R activity in mice.
• Employed designer receptors exclusively activated by designer drugs (DREADDs) to manipulate POMC neuron activity.
• Administered naloxone, an opioid receptor antagonist, systemically and hypothalamically.
• Investigated mitochondrial adaptations in response to CB1R activation.

Main Results:

• CB1R activation increased feeding and, paradoxically, promoted POMC neuron activity.
• Inhibition of POMC neurons via DREADDs diminished CB1R-induced feeding, while activation enhanced it.
• CB1R activation selectively increased hypothalamic β-endorphin release, not α-melanocyte-stimulating hormone.
• Naloxone blocked CB1R-induced feeding, and blocking mitochondrial adaptations abolished CB1R effects.

Conclusions:

• POMC neurons play a previously unrecognized role in promoting feeding stimulated by cannabinoids.
• CB1R-driven feeding involves the release of β-endorphin and requires specific mitochondrial adaptations.
• The study reveals a complex interplay between CB1R signaling, POMC neurons, and feeding regulation.