Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila

Valentina Botero; Bethany A. Stanhope; Elizabeth B. Brown; Eliza C. Grenci; Tamara Boto; Scarlet J. Park; Lanikea B. King; Keith R. Murphy; Kenneth J. Colodner; James A. Walker; Alex C. Keene; William W. Ja; Seth M. Tomchik

doi:10.1038/s41467-021-24505-x

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Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila

Journal article

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Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila

Valentina Botero, Bethany A. Stanhope, Elizabeth B. Brown, Eliza C. Grenci, Tamara Boto, Scarlet J. Park, Lanikea B. King, Keith R. Murphy, Kenneth J. Colodner, James A. Walker, …

Nature communications, Vol.12(1), pp.4285-4285

07/13/2021

DOI: 10.1038/s41467-021-24505-x

PMCID: PMC8277851

PMID: 34257279

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Abstract

Neurofibromatosis type 1 is a chronic multisystemic genetic disorder that results from loss of function in the neurofibromin protein. Neurofibromin may regulate metabolism, though the underlying mechanisms remain largely unknown. Here we show that neurofibromin regulates metabolic homeostasis in Drosophila via a discrete neuronal circuit. Loss of neurofibromin increases metabolic rate via a Ras GAP-related domain-dependent mechanism, increases feeding homeostatically, and alters lipid stores and turnover kinetics. The increase in metabolic rate is independent of locomotor activity, and maps to a sparse subset of neurons. Stimulating these neurons increases metabolic rate, linking their dynamic activity state to metabolism over short time scales. Our results indicate that neurofibromin regulates metabolic rate via neuronal mechanisms, suggest that cellular and systemic metabolic alterations may represent a pathophysiological mechanism in neurofibromatosis type 1, and provide a platform for investigating the cellular role of neurofibromin in metabolic homeostasis. Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in neurofibromin and associated with disruptions in physiology and behavior. Here the authors show that neurofibromin regulates metabolic homeostasis via a discrete brain circuit in a Drosophila model of NF1.

Diseases of the nervous system

Fat metabolism

Feeding behaviour

Neural circuits

Neuroscience

Details

Title: Subtitle: Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila
Creators: Valentina Botero - Scripps Research Institute
Bethany A. Stanhope - Department of Biological Sciences Florida Atlantic University Jupiter FL USA
Elizabeth B. Brown - Department of Biological Sciences Florida Atlantic University Jupiter FL USA
Eliza C. Grenci - Scripps Research Institute
Tamara Boto - Scripps Research Institute
Scarlet J. Park - Scripps Research Institute
Lanikea B. King - Scripps Research Institute
Keith R. Murphy - Scripps Research Institute
Kenneth J. Colodner - Mount Holyoke College
James A. Walker - Broad Institute
Alex C. Keene - Department of Biological Sciences Florida Atlantic University Jupiter FL USA
William W. Ja - Scripps Research Institute
Seth M. Tomchik - Scripps Research Institute
Resource Type: Journal article
Publication Details: Nature communications, Vol.12(1), pp.4285-4285
DOI: 10.1038/s41467-021-24505-x
PMID: 34257279
PMCID: PMC8277851
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: Nature Publishing Group UK
Grant note: ; R01 NS114403; R01 NS097237 / ;
Language: English
Date published: 07/13/2021
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984303855802771

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