Gfral-expressing Neurons Suppress Food Intake via Aversive Pathways
Abstract To determine the function and mechanisms of action for hindbrain neurons that express GFRAL, the receptor for the anorexigenic peptide, GDF-15, we generated Gfralcre and conditional GfralCreERT mice. While signals of infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons, the artificial activation of GfralCre- expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). Additionally, activation of the smaller population of GFRAL neurons captured by the GfralCreERT allele decreased gastric emptying and produced a CTA without suppressing food intake, suggesting that GFRAL neurons primarily modulate gastric physiology and stimulate aversive responses. GFRAL neurons most strongly innervated the parabrachial nucleus (PBN), where they targeted 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 the aversive suppression of nutrient uptake and absorption..
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Preprint| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 15. Dez. Zur Gesamtaufnahme - year:2021 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sabatini, Paul V. [VerfasserIn] |
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| Links: |
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| doi: |
10.1101/2020.05.11.088773 |
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| PPN (Katalog-ID): |
XBI017901014 |
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| 520 | |a Abstract To determine the function and mechanisms of action for hindbrain neurons that express GFRAL, the receptor for the anorexigenic peptide, GDF-15, we generated Gfralcre and conditional GfralCreERT mice. While signals of infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons, the artificial activation of GfralCre- expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). Additionally, activation of the smaller population of GFRAL neurons captured by the GfralCreERT allele decreased gastric emptying and produced a CTA without suppressing food intake, suggesting that GFRAL neurons primarily modulate gastric physiology and stimulate aversive responses. GFRAL neurons most strongly innervated the parabrachial nucleus (PBN), where they targeted 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 the aversive suppression of nutrient uptake and absorption. | ||
| 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 Adams, Jessica M. |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jine |e verfasserin |4 aut | |
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| 700 | 1 | |a Palmiter, Richard D. |e verfasserin |4 aut | |
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| 700 | 1 | |a Seeley, Randy J. |e verfasserin |4 aut | |
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