Therapeutic Potential of FTO Demethylase in Metabolism and Disease Pathways.

The protein journal Pub Date : 2025-02-09 DOI:10.1007/s10930-025-10250-3

Chaitanya Sree Somala, Selvaraj Sathyapriya, Nagaraj Bharathkumar, Thirunavukarasou Anand, Damal Chandrasekar Mathangi, Konda Mani Saravanan

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Abstract

The crucial involvement of the Fat Mass and Obesity-associated (FTO) protein in both metabolic and non-metabolic diseases has been documented since its discovery. This enzyme, known as FTO, is a demethylase that belongs to the 2-oxoglutarate-dependent nucleic acid demethylases. Its primary function is to target N6-methyladenosine (m⁶A) in RNA, which is crucial in regulating RNA stability, processing, and expression. This review facilitates understanding the FTO gene variations linked to Body Mass Index (BMI) and obesity, resulting in increased vulnerability to type 2 diabetes. While prior reviews have already discussed the link between FTO and BMI and its impact on type 2 diabetes, the current review additionally examines the emerging evidence suggesting a direct influence of the FTO gene on metabolism. Additionally, the paper discusses the alternative role of FTO and emphasizes the endophenotypes in neurological circuits and the demethylase function of FTO in neurodegenerative disorders. The review further examines the impact of FTO on several physiological systems and emphasizes the need to study FTO as a potential multitarget for future research and therapies.

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The protein journal

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