GFRAL-expressing neurons suppress food intake via aversive pathways
The TGFβ cytokine family member, GDF-15, reduces food intake and body weight and represents a potential treatment for obesity. Because the brainstem-restricted expression pattern of its receptor, GDNF Family Receptor α-like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake; we generated GfralCre and conditional GfralCreERT mice to visualize and manipulate GFRAL neurons. We found infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons. TRAP-Seq analysis of GFRAL neurons revealed their expression of a wide range of neurotransmitters and neuropeptides. Artificially activating GfralCre -expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), where they target CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated pathophysiologic signals to suppress nutrient uptake and absorption.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:118 |
|---|---|
| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 118(2021), 8 vom: 23. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sabatini, Paul V [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 02.08.2021 Date Revised 14.02.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1073/pnas.2021357118 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM321529316 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM321529316 | ||
| 003 | DE-627 | ||
| 005 | 20240214232300.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.2021357118 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1292.xml |
| 035 | |a (DE-627)NLM321529316 | ||
| 035 | |a (NLM)33593916 | ||
| 035 | |a (PII)e2021357118 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sabatini, Paul V |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a GFRAL-expressing neurons suppress food intake via aversive pathways |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.08.2021 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The TGFβ cytokine family member, GDF-15, reduces food intake and body weight and represents a potential treatment for obesity. Because the brainstem-restricted expression pattern of its receptor, GDNF Family Receptor α-like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake; we generated GfralCre and conditional GfralCreERT mice to visualize and manipulate GFRAL neurons. We found infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons. TRAP-Seq analysis of GFRAL neurons revealed their expression of a wide range of neurotransmitters and neuropeptides. Artificially activating GfralCre -expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), where they target CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated pathophysiologic signals to suppress nutrient uptake and absorption | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CGRP | |
| 650 | 4 | |a GDF-15 | |
| 650 | 4 | |a GFRAL | |
| 650 | 4 | |a area postrema | |
| 650 | 4 | |a obesity | |
| 650 | 7 | |a Glial Cell Line-Derived Neurotrophic Factor Receptors |2 NLM | |
| 650 | 7 | |a Growth Differentiation Factor 15 |2 NLM | |
| 700 | 1 | |a Frikke-Schmidt, Henriette |e verfasserin |4 aut | |
| 700 | 1 | |a Arthurs, Joe |e verfasserin |4 aut | |
| 700 | 1 | |a Gordian, Desiree |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Anita |e verfasserin |4 aut | |
| 700 | 1 | |a Rupp, Alan C |e verfasserin |4 aut | |
| 700 | 1 | |a Adams, Jessica M |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jine |e verfasserin |4 aut | |
| 700 | 1 | |a Beck Jørgensen, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Olson, David P |e verfasserin |4 aut | |
| 700 | 1 | |a Palmiter, Richard D |e verfasserin |4 aut | |
| 700 | 1 | |a Myers, Martin G |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Seeley, Randy J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d 1915 |g 118(2021), 8 vom: 23. Feb. |w (DE-627)NLM000008982 |x 1091-6490 |7 nnns |
| 773 | 1 | 8 | |g volume:118 |g year:2021 |g number:8 |g day:23 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.2021357118 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 118 |j 2021 |e 8 |b 23 |c 02 | ||