Universität zu Köln

Borgmann, Diba, Ciglieri, Elisa, Biglari, Nasim, Brandt, Claus ORCID: 0000-0002-7871-7437, Cremer, Anna Lena, Backes, Heiko, Tittgemeyer, Marc, Wunderlich, F. Thomas, Bruning, Jens C. and Fenselau, Henning (2021). Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism. Cell Metab., 33 (7). S. 1466 - 1491. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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Abstract

Sensory neurons relay gut-derived signals to the brain, yet the molecular and functional organization of distinct populations remains unclear. Here, we employed intersectional genetic manipulations to probe the feeding and glucoregulatory function of distinct sensory neurons. We reconstruct the gut innervation patterns of numerous molecularly defined vagal and spinal afferents and identify their downstream brain targets. Bidirectional chemogenetic manipulations, coupled with behavioral and circuit mapping analysis, demonstrated that gut-innervating, glucagon-like peptide 1 receptor (GLP1R)-expressing vagal afferents relay anorexigenic signals to parabrachial nucleus neurons that control meal termination. Moreover, GLP1R vagal afferent activation improves glucose tolerance, and their inhibition elevates blood glucose levels independent of food intake. In contrast, gut-innervating, GPR65-expressing vagal afferent stimulation increases hepatic glucose production and activates parabrachial neurons that control normoglycemia, but they are dispensable for feeding regulation. Thus, distinct gut-innervating sensory neurons differentially control feeding and glucoregulatory neurocircuits and may provide specific targets for metabolic control.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Borgmann, Diba UNSPECIFIED UNSPECIFIED UNSPECIFIED Ciglieri, Elisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Biglari, Nasim UNSPECIFIED UNSPECIFIED UNSPECIFIED Brandt, Claus UNSPECIFIED orcid.org/0000-0002-7871-7437 UNSPECIFIED Cremer, Anna Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Backes, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Tittgemeyer, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruning, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fenselau, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-573502
DOI:	10.1016/j.cmet.2021.05.002
Journal or Publication Title:	Cell Metab.
Volume:	33
Number:	7
Page Range:	S. 1466 - 1491
Date:	2021
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1932-7420
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOOD-INTAKE; AFFERENT INNERVATION; SMOOTH-MUSCLE; ATTENUATES SUPPRESSION; GENETIC IDENTIFICATION; NEURAL CIRCUIT; MEAL SIZE; VAGAL; RAT; RESPONSES Multiple languages Cell Biology; Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57350