mTORC1 Signaling in AgRP Neurons Is Not Required to Induce Major Neuroendocrine Adaptations to Food Restriction
Hypothalamic mTORC1 signaling is involved in nutrient sensing. Neurons that express the agouti-related protein (AgRP) are activated by food restriction and integrate interoceptive and exteroceptive signals to control food intake, energy expenditure, and other metabolic responses. To determine whethe...
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MDPI AG
2023-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/20/2442 |
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| author | Gabriel O. de Souza Pryscila D. S. Teixeira Niels O. S. Câmara Jose Donato |
| author_facet | Gabriel O. de Souza Pryscila D. S. Teixeira Niels O. S. Câmara Jose Donato |
| author_sort | Gabriel O. de Souza |
| collection | DOAJ |
| description | Hypothalamic mTORC1 signaling is involved in nutrient sensing. Neurons that express the agouti-related protein (AgRP) are activated by food restriction and integrate interoceptive and exteroceptive signals to control food intake, energy expenditure, and other metabolic responses. To determine whether mTORC1 signaling in AgRP neurons is necessary for regulating energy and glucose homeostasis, especially in situations of negative energy balance, mice carrying ablation of the <i>Raptor</i> gene exclusively in AgRP-expressing cells were generated. AgRP<sup>ΔRaptor</sup> mice showed no differences in body weight, fat mass, food intake, or energy expenditure; however, a slight improvement in glucose homeostasis was observed compared to the control group. When subjected to 5 days of food restriction (40% basal intake), AgRP<sup>ΔRaptor</sup> female mice lost less lean body mass and showed a blunted reduction in energy expenditure, whereas AgRP<sup>ΔRaptor</sup> male mice maintained a higher energy expenditure compared to control mice during the food restriction and 5 days of refeeding period. AgRP<sup>ΔRaptor</sup> female mice did not exhibit the food restriction-induced increase in serum corticosterone levels. Finally, although hypothalamic fasting- or refeeding-induced Fos expression showed no differences between the groups, AgRP<sup>ΔRaptor</sup> mice displayed increased hyperphagia during refeeding. Thus, some metabolic and neuroendocrine responses to food restriction are disturbed in AgRP<sup>ΔRaptor</sup> mice. |
| first_indexed | 2024-03-10T21:21:39Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T21:21:39Z |
| publishDate | 2023-10-01 |
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| series | Cells |
| spelling | doaj.art-73246cd9663645c08b147b6794552ab42023-11-19T16:02:11ZengMDPI AGCells2073-44092023-10-011220244210.3390/cells12202442mTORC1 Signaling in AgRP Neurons Is Not Required to Induce Major Neuroendocrine Adaptations to Food RestrictionGabriel O. de Souza0Pryscila D. S. Teixeira1Niels O. S. Câmara2Jose Donato3Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo 05508-000, SP, BrazilDepartamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo 05508-000, SP, BrazilDepartamento de Imunologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo 05508-000, SP, BrazilDepartamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo 05508-000, SP, BrazilHypothalamic mTORC1 signaling is involved in nutrient sensing. Neurons that express the agouti-related protein (AgRP) are activated by food restriction and integrate interoceptive and exteroceptive signals to control food intake, energy expenditure, and other metabolic responses. To determine whether mTORC1 signaling in AgRP neurons is necessary for regulating energy and glucose homeostasis, especially in situations of negative energy balance, mice carrying ablation of the <i>Raptor</i> gene exclusively in AgRP-expressing cells were generated. AgRP<sup>ΔRaptor</sup> mice showed no differences in body weight, fat mass, food intake, or energy expenditure; however, a slight improvement in glucose homeostasis was observed compared to the control group. When subjected to 5 days of food restriction (40% basal intake), AgRP<sup>ΔRaptor</sup> female mice lost less lean body mass and showed a blunted reduction in energy expenditure, whereas AgRP<sup>ΔRaptor</sup> male mice maintained a higher energy expenditure compared to control mice during the food restriction and 5 days of refeeding period. AgRP<sup>ΔRaptor</sup> female mice did not exhibit the food restriction-induced increase in serum corticosterone levels. Finally, although hypothalamic fasting- or refeeding-induced Fos expression showed no differences between the groups, AgRP<sup>ΔRaptor</sup> mice displayed increased hyperphagia during refeeding. Thus, some metabolic and neuroendocrine responses to food restriction are disturbed in AgRP<sup>ΔRaptor</sup> mice.https://www.mdpi.com/2073-4409/12/20/2442agouti-related proteinfood intakehypothalamusmammalian target of rapamycinmouseraptor |
| spellingShingle | Gabriel O. de Souza Pryscila D. S. Teixeira Niels O. S. Câmara Jose Donato mTORC1 Signaling in AgRP Neurons Is Not Required to Induce Major Neuroendocrine Adaptations to Food Restriction Cells agouti-related protein food intake hypothalamus mammalian target of rapamycin mouse raptor |
| title | mTORC1 Signaling in AgRP Neurons Is Not Required to Induce Major Neuroendocrine Adaptations to Food Restriction |
| title_full | mTORC1 Signaling in AgRP Neurons Is Not Required to Induce Major Neuroendocrine Adaptations to Food Restriction |
| title_fullStr | mTORC1 Signaling in AgRP Neurons Is Not Required to Induce Major Neuroendocrine Adaptations to Food Restriction |
| title_full_unstemmed | mTORC1 Signaling in AgRP Neurons Is Not Required to Induce Major Neuroendocrine Adaptations to Food Restriction |
| title_short | mTORC1 Signaling in AgRP Neurons Is Not Required to Induce Major Neuroendocrine Adaptations to Food Restriction |
| title_sort | mtorc1 signaling in agrp neurons is not required to induce major neuroendocrine adaptations to food restriction |
| topic | agouti-related protein food intake hypothalamus mammalian target of rapamycin mouse raptor |
| url | https://www.mdpi.com/2073-4409/12/20/2442 |
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