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Hypothalamic FTO is associated with the regulation of energy intake not feeding reward.
BMC Neurosci. 2009 Oct 27; 10:129.BN

Abstract

BACKGROUND

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.

RESULTS

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.

CONCLUSION

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.

Authors+Show Affiliations

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden. olsze005@umn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19860904

Citation

Olszewski, Pawel K., et al. "Hypothalamic FTO Is Associated With the Regulation of Energy Intake Not Feeding Reward." BMC Neuroscience, vol. 10, 2009, p. 129.
Olszewski PK, Fredriksson R, Olszewska AM, et al. Hypothalamic FTO is associated with the regulation of energy intake not feeding reward. BMC Neurosci. 2009;10:129.
Olszewski, P. K., Fredriksson, R., Olszewska, A. M., Stephansson, O., Alsiö, J., Radomska, K. J., Levine, A. S., & Schiöth, H. B. (2009). Hypothalamic FTO is associated with the regulation of energy intake not feeding reward. BMC Neuroscience, 10, 129. https://doi.org/10.1186/1471-2202-10-129
Olszewski PK, et al. Hypothalamic FTO Is Associated With the Regulation of Energy Intake Not Feeding Reward. BMC Neurosci. 2009 Oct 27;10:129. PubMed PMID: 19860904.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypothalamic FTO is associated with the regulation of energy intake not feeding reward. AU - Olszewski,Pawel K, AU - Fredriksson,Robert, AU - Olszewska,Agnieszka M, AU - Stephansson,Olga, AU - Alsiö,Johan, AU - Radomska,Katarzyna J, AU - Levine,Allen S, AU - Schiöth,Helgi B, Y1 - 2009/10/27/ PY - 2009/09/23/received PY - 2009/10/27/accepted PY - 2009/10/29/entrez PY - 2009/10/29/pubmed PY - 2009/12/16/medline SP - 129 EP - 129 JF - BMC neuroscience JO - BMC Neurosci VL - 10 N2 - BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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. SN - 1471-2202 UR - https://www.unboundmedicine.com/medline/citation/19860904/Hypothalamic_FTO_is_associated_with_the_regulation_of_energy_intake_not_feeding_reward_ L2 - https://bmcneurosci.biomedcentral.com/articles/10.1186/1471-2202-10-129 DB - PRIME DP - Unbound Medicine ER -