Alpha-ketoglutarate-dependent with an increased risk of obesity, characterized by

 

Alpha-ketoglutarate-dependent dioxygenase (FTO) is an enzyme, which is encoded by the FTO gene located on chromosome 16. It is one of the first mRNA demethylase that has been identified. It is also one of the homologs in the AlkB family proteins. Specific variants of this gene appear to be associated with obesity. This gene is also known as the fat mass and obesity associated gene. The FTO mutation can be implicated in other health conditions related such as facial dysmorphism, growth retardation, and delay in development.

A bioinformatics analysis conducted by Gerken et al showed that FTO shares sequence motifs with Fe(II)- and 2- oxoglutarate-dependent oxygenase’s(2OG).2OG oxygenase’s are involved in diverse processes, including DNA repair, fatty acid metabolism, and posttranslational modifications. (Gerken et al, 2009). Recent studies have shown the strong association of a number of SNPs in intron 1 of the human FTO gene with an increased risk of obesity, characterized by an increase in body max index due to Fat mass rather than lean mass that is seen in children as early as age seven. (Gerken et al) . The mechanism by which this genetic variability relates to obesity remains obscure. The studies indicate that the function of FTO is unknown and its protein has no identified structural domain to other proteins that could be used to predict its function (Pulido et al 2007)

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The FTO gene is expressed in many tissues such as the central nervous system, the hypothalamus, the brainstem and extended amygdala. (Fredriksson et al, 2008). In a body panel on rats conducted by Fredriksson et al, they found that the expression of FTO in the hypothalamus is up-regulated during starvation and is negatively correlated with orexigenic peptide GALP which is simulated in the uptake of food. (Fredriksson et al, 2008.). Furthermore, another study conducted by Olszewski et al,  had similar results with the study conducted by Fredriksson, this study wanted to determine if hypothalamic FTO is involved in energy-dependent overconsumption of food. The study concluded that FTO mRNA is present mainly in sites related to hunger/satiation and that changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward (Olszewski et al 2009).

             Wiemerslage et al recently conducted a study to examine how the obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content using fMRI machine. The study showed that the people with the FTO risk allele had increased activity compared to the people who had the non-risk genotype. (Wiemerslage et al. 2016)

With further research in the future into the FTO SNP, it can help us to develop strategies for weight-loss treatment and understand the genetics behind individual feeding behaviours.