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Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control.

Cell metabolism | 2017

Proopiomelanocortin (POMC) neurons are critical sensors of nutrient availability implicated in energy balance and glucose metabolism control. However, the precise mechanisms underlying nutrient sensing in POMC neurons remain incompletely understood. We show that mitochondrial dynamics mediated by Mitofusin 1 (MFN1) in POMC neurons couple nutrient sensing with systemic glucose metabolism. Mice lacking MFN1 in POMC neurons exhibited defective mitochondrial architecture remodeling and attenuated hypothalamic gene expression programs during the fast-to-fed transition. This loss of mitochondrial flexibility in POMC neurons bidirectionally altered glucose sensing, causing abnormal glucose homeostasis due to defective insulin secretion by pancreatic β cells. Fed mice lacking MFN1 in POMC neurons displayed enhanced hypothalamic mitochondrial oxygen flux and reactive oxygen species generation. Central delivery of antioxidants was able to normalize the phenotype. Collectively, our data posit MFN1-mediated mitochondrial dynamics in POMC neurons as an intrinsic nutrient-sensing mechanism and unveil an unrecognized link between this subset of neurons and insulin release.

Pubmed ID: 28591639 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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Tom20 (FL-145) Antibody (antibody)

RRID:AB_2207533

This polyclonal targets Tom20 (FL-145)

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Proopiomelanocortin Precursor (POMC) (27-52) (antibody)

RRID:AB_2307442

This polyclonal targets Aminoacids 27-52 of porcine Pro-opiomelanocortin peptide

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Mfn1 (H-65) (antibody)

RRID:AB_2250540

This polyclonal targets MFN1

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c-Fos Antibody (4) (antibody)

RRID:AB_2106783

This polyclonal targets FOS

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Mitofusin 2 antibody (antibody)

RRID:AB_2142629

This monoclonal targets Mfn2

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Insulin (antibody)

RRID:AB_10013624

This polyclonal targets Porcine pancreatic insulin

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limmaGUI (software resource)

RRID:SCR_001306

Software package for a Graphical User Interface for the limma Microarray package.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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DAVID (software resource)

RRID:SCR_003033

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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