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InsR/FoxO1 signaling curtails hypothalamic POMC neuron number
Leona Plum1, Hua V Lin, Kumiko S Aizawa
1Naomi Berrie Diabetes Center, Department of Medicine, Columbia University Medical Center, New York, New York, United States of America.
Insulin receptor (InsR) signaling impacts hypothalamic POMC neuron development. Impaired InsR signaling increases POMC neuron numbers in adults, a process partly regulated by FoxO1 transcription factor.
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- Insulin receptor (InsR) signaling is crucial for hypothalamic feeding circuits.
- The role of InsR/FoxO1 signaling in POMC neuron development and maintenance is not fully understood.
Purpose of the Study:
- To investigate the role of InsR/FoxO1 signaling in the development and maintenance of hypothalamic POMC neurons.
- To determine the cell-autonomous function of InsR/FoxO1 in regulating POMC neuron number.
Main Methods:
- Utilized mouse models with impaired hypothalamic InsR signaling.
- Surveyed POMC neuron numbers in different genetic backgrounds.
- Examined POMC neuron number in mice with POMC-specific deletion of FoxO1.
Main Results:
- Hypothalamic InsR ablation increased adult POMC neuron numbers by 25%, particularly in the arcuate nucleus.
- Restoring InsR in POMC neurons partially reversed this increase.
- POMC-specific FoxO1 deletion decreased POMC neuron numbers by 23%, indicating a cell-autonomous role.
Conclusions:
- InsR/FoxO1 signaling plays a cell-autonomous role in regulating POMC neuron number, independent of its role in Pomc transcription.
- This signaling pathway is critical for the development and maintenance of hypothalamic feeding circuits.
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