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FTO expression is regulated by availability of essential amino acids

International Journal of Obesity volume 37, pages 744–747 (2013)Cite this article

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Abstract

Genome-wide association studies have revealed that single nucleotide polymorphisms in fat mass and obesity-associated transcript (FTO) are robustly associated with body mass index and obesity. Expression of Fto in the hypothalamic arcuate nucleus is bidirectionally regulated as a function of nutritional status; decreasing following a 48-h fast and increasing after 10-week exposure to a high-fat diet. Here, we utilize an in vitro approach to determine which nutrients could regulate FTO levels at a cellular level. Using mouse and human cell lines, we find that FTO levels are not influenced by serum starvation. We demonstrate, however, that both glucose and total amino-acid deprivation regulates FTO expression. In particular, we have found that FTO mRNA and protein levels are dramatically downregulated by total amino-acid deprivation in mouse hypothalamic N46 cells, mouse embryonic fibroblasts and in human HEK293 cells. The drop rate of Fto mRNA is faster than its rate of natural degradation, pointing to regulation at the transcriptional level, which is reversible upon amino-acid replacement. Strikingly, this downregulation was seen only with essential amino-acid deficiency and not nonessential amino acids. These data suggest that FTO might have a role in the sensing of essential amino-acid availability.

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Acknowledgements

This study was supported by the UK Medical Research Council Center for Obesity and Related Metabolic Disorders (MRC-CORD), the EU FP7-HEALTH-2009-241592 EurOCHIP and EU FP7-HEALTH-266408 (Full4Health).

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Authors and Affiliations

  1. University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK

    M K Cheung, P Gulati, S O'Rahilly & G S H Yeo

  2. NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK

    M K Cheung, P Gulati, S O'Rahilly & G S H Yeo

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  1. M K Cheung
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  2. P Gulati
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  3. S O'Rahilly
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  4. G S H Yeo
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Correspondence to G S H Yeo.

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Supplementary Information accompanies the paper on International Journal of Obesity website

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Cheung, M., Gulati, P., O'Rahilly, S. et al. FTO expression is regulated by availability of essential amino acids. Int J Obes 37, 744–747 (2013). https://doi.org/10.1038/ijo.2012.77

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