Programming effects of FTO in the development of obesity

Abstract

It is becoming increasingly recognized that early-life nutritional, metabolic and environmental factors can have a long-term impact on the early onset of obesity, type 2 diabetes and cardiovascular diseases. Numerous experimental and epidemiological observations support the concept that an individual's response to their adult lifestyle and nutritional environment depends not only on their genetic susceptibility but also on their previous early-life experiences. The current research challenge is to determine the primary pathways contributing to 'non- or epi-genetic' causes of excess adult weight gain and adiposity. Evidence from the fields of genetic epidemiology, life course modelling and diet-induced foetal programming all support a role for the FTO gene in this complex biological interaction. It may provide a missing link in the developmental regulation of energy metabolism. Our review therefore considers the role of the FTO gene in the early-life determination of body weight, body composition and energy balance. We will summarize current knowledge on FTO biology combining human genetic epidemiology, molecular models and findings from animal studies. Notably, we will focus on the role of FTO in energy balance in humans, the importance of FTO polymorphisms in childhood growth and the impact of foetal nutrition. Ultimately, we propose a new hypothesis for future research designed to understand the role of FTO in setting gene expression in metabolically active tissues.

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men

“…Moreover, in animal model’s overexpression of FTO increases the expression of the RUNX1T1 transcription factor in embryonic fibroblasts stimulating the number of adipocytes [57]. Knowing that FTO expression can modulate obesity onset [19,58] due to its stronger expression during childhood, it is feasible to think that throughout adulthood the high consumption of foods that stimulate FTO overexpression would contribute to the high incidence of obesity, and hence PCa risk. Unfortunately, we did not have access to the lifetime health records of our participants, so we are unable to establish the timeline for obesity onset in our cohort.…”

Milk’s Role as an Epigenetic Regulator in Health and Disease

“…Perinatal programming of energy intake and eating behavior provide a potential mechanism linking early life influences with later obesity, T2DM and cardiovascular disease [281]. Notably, single nucleotide polymorphisms of FTO , which are associated with increased FTO expression increase the risk for obesity and T2DM [282,283,284,285,286,287]. FTO expression is not only controlled by the nucleotide sequence but also by epigenetic regulation of FTO .…”

Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects

“…This SNP is known to predispose to obesity, type II diabetes and cardiovascular diseases and has also been linked to psychological disorders. [55][56][57][58] A longitudinal study in Brazil found a 0.07 kg/m 2 /year weight gain for each additional risk allele. 59 It has been previously reported that the overall risk of obesity is increased~1.3-fold per risk allele.…”