Enteroendocrine cell types that drive food reward and aversion

Abstract
Data availability
Article and author information
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Abstract

Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the principal chemosensors in the GI tract, but investigation of their role in behavior has been limited by the difficulty of selectively targeting these cells in vivo. Here we describe an intersectional genetic approach for manipulating EEC subtypes in behaving mice. We show that multiple EEC subtypes inhibit food intake but have different effects on learning. Conditioned flavor preference is driven by release of cholecystokinin whereas conditioned taste aversion is mediated by serotonin and substance P. These positive and negative valence signals are transmitted by vagal and spinal afferents, respectively. These findings establish a cellular basis for how chemosensing in the gut drives learning about food.

Data availability

Source data is included in the manuscript. RNA-seq data is available from the Gene Expression Omnibus (GSE203200). Villin-Flp mice have been deposited at Jackson laboratory.

The following data sets were generated

1. Bai L
2. Knight Z
3. Yu S
(2022) Enteroendocrine cell types that drive food reward and aversion
NCBI Gene Expression Omnibus, GSE203200.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?&acc=GSE203200

The following previously published data sets were used

1. Gehart H
2. van Es JH
3. Hamer K
4. Beumer J
5. Kretzschmar K
6. Dekkers JF
7. Rios A
8. Clevers H
(2018) Identification of functional enteroendocrine regulators by real-time single-cell differentiation mapping
NCBI Gene Expression Omnibus, GSE113561.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113561

Article and author information

Author details

Ling Bai

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Nilla Sivakumar

Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Shenliang Yu

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Sheyda Mesgarzadeh

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0138-5566
Tom Ding

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Truong Ly

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Timothy V Corpuz

Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
James CR Grove

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Brooke C Jarvie

Department of Physiology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Zachary A Knight

Department of Physiology, University of California, San Francisco, San Francisco, United States

For correspondence
zachary.knight@ucsf.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7621-1478

Funding

National Institutes of Health (R01-DK106399)

Zachary A Knight

National Institutes of Health (RF1-NS116626)

Zachary A Knight

Howard Hughes Medical Institute (Investigator)

Zachary A Knight

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental protocols were approved by the University of California, San Francisco IACUC (protocol #AN179674) following the National Institutes of Health guidelines for the Care and Use of Laboratory Animals.

Copyright

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.