Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss

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Abstract

Molecular and cellular processes in neurons are critical for sensing and responding to energy deficit states, such as during weight-loss. AGRP neurons are a key hypothalamic population that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss, and here we report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived young adult mice. For comparison, we also analyzed POMC neurons, an intermingled population that suppresses appetite and body weight. We find that AGRP neurons are considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion channels, neuropeptides, and receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders.

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Fredrick E Henry

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States

Competing interests
The authors declare that no competing interests exist.
Ken Sugino

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States

Competing interests
The authors declare that no competing interests exist.
Adam Tozer

Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Tiago Branco

Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Scott M Sternson

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States

For correspondence
sternsons@janelia.hhmi.org

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experimental protocols were conducted according to U.S. National Institutes of Health guidelines for animal research and approved by the Institutional Animal Care and Use Committee at Janelia Research Campus under protocol number 13-92. Experiments conducted in the UK were licensed (PPL 70/7652) under the UK Animals (Scientific Procedures) Act of 1986 following local ethical approval. All surgery was performed under isoflurance anesthesia to minimize suffering.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.