Pillar 1 - FTO (new thread), page-25

This study completed in November 2020 describes how FTO influences both obesity and cancer. While most of us may have a basic understanding of how Bisantrene may be used at low dose to inhibit FTO for cancer, I’m not sure I have seen anything with regards to Obesity – another significant challenge in the obesogenic world in which we live.

This article states that FTO proteins are widely involved in adipogenesis (the growth of adipose tissue – commonly known as fat). It does this by influencing the m⁶A level of hormones that relate to eating or molecules related to adipogenesis.

FTOover-expression limited the m⁶A modification of ghrelin mRNA in cell models and increased ghrelin mRNA and peptide levels concomitantly. Ghrelin is a hormone produced by the enteroendocrine cells of the GI tract and is commonly known as the “hunger hormone”, as it increases food intake. Ghrelin levels are highest before meals when hungry and return to lower levels after mealtimes. If FTO over-expression increases ghrelin mRNA and peptide levels, then it may also lead to increased hunger signals being sent to the brain.

Substantialevidence demonstrates that FTO regulates pre-adipocyte (before it’s a fat cell)differentiation by regulating the exonic splicing of the adipogenic regulatorRUNX1T1 by influencing m⁶A levels around splice sites. Also, FTO influences adipogenesis by regulating mitotic clonal expansion (MCE), a prerequisite for adipocyte differentiation that occurs within 48 h of adipogenic stimulation. Lastly, FTO regulated adipogenesis by dominating cell cycle proteins.

Obesity:

The global weight management market is estimated at USD$262.9B in 2020 and is expected to reach USD $423.2 B by 2027. I can’t find a percentage of which is spent on pharmaceuticals to help with weight loss, but I’m assuming it’s going to be a rough percentage of that. Current weight loss drugs on the market include Orlistat (decreases fat absorption), Lorcaserin (induces satiety), Phentermine-topiramate (decreases appetite and induces satiety), and Saxenda (decreases appetite and induces satiety). While these drugs may be effective, they come with a host of potential side effects and some of them some unpleasant gastro-intestinal symptoms.