Steculorum, Sophie M., Ruud, Johan, Karakasilioti, Ismene, Backes, Heiko, Ruud, Linda Engstroem, Timper, Katharina, Hess, Martin E., Tsaousidou, Eva ORCID: 0000-0003-2751-1911, Mauer, Jan ORCID: 0000-0002-0189-5876, Vogt, Merly C., Paeger, Lars ORCID: 0000-0001-8716-3483, Bremser, Stephan, Klein, Andreas C., Morgan, Donald A., Frommolt, Peter ORCID: 0000-0002-1966-8014, Brinkkoetter, Paul T., Hammerschmidt, Philipp, Benzing, Thomas, Rahmouni, Kamal ORCID: 0000-0001-5136-6748, Wunderlich, F. Thomas, Kloppenburg, Peter and Bruening, Jens C. (2016). AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue. Cell, 165 (1). S. 125 - 139. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP -> LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP -> anterior bed nucleus of the stria terminalis (aBNST)(vl) projections, distinct from AgRP -> aBNST(dm) projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Steculorum, Sophie M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruud, JohanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karakasilioti, IsmeneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Backes, HeikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruud, Linda EngstroemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timper, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, Martin E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tsaousidou, EvaUNSPECIFIEDorcid.org/0000-0003-2751-1911UNSPECIFIED
Mauer, JanUNSPECIFIEDorcid.org/0000-0002-0189-5876UNSPECIFIED
Vogt, Merly C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paeger, LarsUNSPECIFIEDorcid.org/0000-0001-8716-3483UNSPECIFIED
Bremser, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, Andreas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgan, Donald A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frommolt, PeterUNSPECIFIEDorcid.org/0000-0002-1966-8014UNSPECIFIED
Brinkkoetter, Paul T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hammerschmidt, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahmouni, KamalUNSPECIFIEDorcid.org/0000-0001-5136-6748UNSPECIFIED
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kloppenburg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-281036
DOI: 10.1016/j.cell.2016.02.044
Journal or Publication Title: Cell
Volume: 165
Number: 1
Page Range: S. 125 - 139
Date: 2016
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POMC NEURONS; GLUCOSE-HOMEOSTASIS; NPY/AGRP NEURONS; TRANSGENIC MICE; NEURAL CIRCUIT; ACTIVATION; LEPTIN; SUPPRESSION; OBESITY; CNSMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28103

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