AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish
Neuronal circuits regulating appetite are dominated by arcuate nucleus neurons, which include appetite-promoting and -suppressing neurons that release the orexigenic neuropeptide agouti-related protein (AgRP) and anorexigenic neuropeptide pro-opiomelanocortin, respectively, to compete for melanocort...
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/499 |
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| author | Chiu-Ya Lin Kun-Yun Yeh Hsin-Hung Lai Guor Mour Her |
| author_facet | Chiu-Ya Lin Kun-Yun Yeh Hsin-Hung Lai Guor Mour Her |
| author_sort | Chiu-Ya Lin |
| collection | DOAJ |
| description | Neuronal circuits regulating appetite are dominated by arcuate nucleus neurons, which include appetite-promoting and -suppressing neurons that release the orexigenic neuropeptide agouti-related protein (AgRP) and anorexigenic neuropeptide pro-opiomelanocortin, respectively, to compete for melanocortin receptors to modulate feeding behavior. In this study, we expressed novel <i>agrp</i> promoters, including different lengths of the 5’ flanking regions of the <i>agrp</i> gene (4749 bp) in the zebrafish genome. We used the <i>agrp</i> promoter to derive the enhanced green fluorescent protein (EGFP)-nitroreductase (NTR) fusion protein, allowing expression of the green fluorescence signal in the AgRP neurons. Then, we treated the transgenic zebrafish AgRP4.7<sup>NTR</sup> (Tg [<i>agrp-EGFP-NTR</i>]) with metronidazole to ablate the AgRP neurons in the larvae stage and observed a decline in their appetite and growth. The expression of most orexigenic and growth hormone/insulin-like growth factor axis genes decreased, whereas that of several anorexigenic genes increased. Our findings demonstrate that AgRP is a critical regulator of neuronal signaling for zebrafish appetite and energy intake control. Thus, AgRP4.7<sup>NTR</sup> can be used as a drug-screening platform for therapeutic targets to treat human appetite disorders, including obesity. Furthermore, the unique <i>agrp</i> promoter we identified can be a powerful tool for research on AgRP neurons, especially AgRP neuron-mediated pathways in the hypothalamus, and appetite. |
| first_indexed | 2024-03-11T09:06:54Z |
| format | Article |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-11T09:06:54Z |
| publishDate | 2023-02-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-5fc61e880b0944a5878bf4e95d98ca902023-11-16T19:19:07ZengMDPI AGBiomedicines2227-90592023-02-0111249910.3390/biomedicines11020499AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval ZebrafishChiu-Ya Lin0Kun-Yun Yeh1Hsin-Hung Lai2Guor Mour Her3Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung City 202, TaiwanDivision of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung City 204, TaiwanInstitute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112, TaiwanInstitute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112, TaiwanNeuronal circuits regulating appetite are dominated by arcuate nucleus neurons, which include appetite-promoting and -suppressing neurons that release the orexigenic neuropeptide agouti-related protein (AgRP) and anorexigenic neuropeptide pro-opiomelanocortin, respectively, to compete for melanocortin receptors to modulate feeding behavior. In this study, we expressed novel <i>agrp</i> promoters, including different lengths of the 5’ flanking regions of the <i>agrp</i> gene (4749 bp) in the zebrafish genome. We used the <i>agrp</i> promoter to derive the enhanced green fluorescent protein (EGFP)-nitroreductase (NTR) fusion protein, allowing expression of the green fluorescence signal in the AgRP neurons. Then, we treated the transgenic zebrafish AgRP4.7<sup>NTR</sup> (Tg [<i>agrp-EGFP-NTR</i>]) with metronidazole to ablate the AgRP neurons in the larvae stage and observed a decline in their appetite and growth. The expression of most orexigenic and growth hormone/insulin-like growth factor axis genes decreased, whereas that of several anorexigenic genes increased. Our findings demonstrate that AgRP is a critical regulator of neuronal signaling for zebrafish appetite and energy intake control. Thus, AgRP4.7<sup>NTR</sup> can be used as a drug-screening platform for therapeutic targets to treat human appetite disorders, including obesity. Furthermore, the unique <i>agrp</i> promoter we identified can be a powerful tool for research on AgRP neurons, especially AgRP neuron-mediated pathways in the hypothalamus, and appetite.https://www.mdpi.com/2227-9059/11/2/499AgRP neuronneuronal ablationorexigenichypothalamusappetite |
| spellingShingle | Chiu-Ya Lin Kun-Yun Yeh Hsin-Hung Lai Guor Mour Her AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish Biomedicines AgRP neuron neuronal ablation orexigenic hypothalamus appetite |
| title | AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish |
| title_full | AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish |
| title_fullStr | AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish |
| title_full_unstemmed | AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish |
| title_short | AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish |
| title_sort | agrp neuron specific ablation represses appetite energy intake and somatic growth in larval zebrafish |
| topic | AgRP neuron neuronal ablation orexigenic hypothalamus appetite |
| url | https://www.mdpi.com/2227-9059/11/2/499 |
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