Hypothalamic FTO is associated with the regulation of energy intake not feeding reward
<p>Abstract</p> <p>Background</p> <p>Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. W...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-10-01
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| Series: | BMC Neuroscience |
| Online Access: | http://www.biomedcentral.com/1471-2202/10/129 |
| _version_ | 1818676393098084352 |
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| author | Radomska Katarzyna J Alsiö Johan Stephansson Olga Olszewska Agnieszka M Fredriksson Robert Olszewski Pawel K Levine Allen S Schiöth Helgi B |
| author_facet | Radomska Katarzyna J Alsiö Johan Stephansson Olga Olszewska Agnieszka M Fredriksson Robert Olszewski Pawel K Levine Allen S Schiöth Helgi B |
| author_sort | Radomska Katarzyna J |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH) was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal.</p> <p>Results</p> <p>Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin.</p> <p>Conclusion</p> <p>We conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism.</p> |
| first_indexed | 2024-12-17T08:42:45Z |
| format | Article |
| id | doaj.art-16acc8abec3146c0ad190eea70ea0629 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-17T08:42:45Z |
| publishDate | 2009-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-16acc8abec3146c0ad190eea70ea06292022-12-21T21:56:17ZengBMCBMC Neuroscience1471-22022009-10-0110112910.1186/1471-2202-10-129Hypothalamic FTO is associated with the regulation of energy intake not feeding rewardRadomska Katarzyna JAlsiö JohanStephansson OlgaOlszewska Agnieszka MFredriksson RobertOlszewski Pawel KLevine Allen SSchiöth Helgi B<p>Abstract</p> <p>Background</p> <p>Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH) was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal.</p> <p>Results</p> <p>Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin.</p> <p>Conclusion</p> <p>We conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism.</p>http://www.biomedcentral.com/1471-2202/10/129 |
| spellingShingle | Radomska Katarzyna J Alsiö Johan Stephansson Olga Olszewska Agnieszka M Fredriksson Robert Olszewski Pawel K Levine Allen S Schiöth Helgi B Hypothalamic FTO is associated with the regulation of energy intake not feeding reward BMC Neuroscience |
| title | Hypothalamic FTO is associated with the regulation of energy intake not feeding reward |
| title_full | Hypothalamic FTO is associated with the regulation of energy intake not feeding reward |
| title_fullStr | Hypothalamic FTO is associated with the regulation of energy intake not feeding reward |
| title_full_unstemmed | Hypothalamic FTO is associated with the regulation of energy intake not feeding reward |
| title_short | Hypothalamic FTO is associated with the regulation of energy intake not feeding reward |
| title_sort | hypothalamic fto is associated with the regulation of energy intake not feeding reward |
| url | http://www.biomedcentral.com/1471-2202/10/129 |
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