Intracellular and tissue specific expression of FTO protein in pig: changes with age, energy intake and metabolic status

Genome-wide association studies in the FTO gene have identified SNPs correlating with obesity and type 2 diabetes. In mice, lack of Fto function leads to intrauterine growth retardation and lean phenotype, whereas in human it is lethal. The aim of this study in a pig model was to determine the
localization of the FTO protein in different tissues and cell compartments, in order to investigate
potential targets of FTO action. To better understand physiological role of FTO protein, its expression
was studied in pigs of different age, metabolic status and nutrition, using both microscopic methods
and Western blot analysis. For the first time, FTO protein was found in vivo in the cytoplasm, of not all,
but specific tissues and cells e.g. in the pancreatic β-cells. Abundant FTO protein expression was found
in the cerebellum, salivary gland and kidney of adult pigs. No FTO protein expression was detected in
blood, saliva, and bile, excluding its role in cell-to-cell communication. In the pancreas, FTO protein
expression was positively associated with energy intake, whereas in the muscles it was strictly agerelated.
In IUGR piglets, FTO protein expression was much higher in the cerebellum and kidneys, as
compared to normal birth body weight littermates. In conclusion, our data suggest that FTO protein
may play a number of distinct, yet unknown intracellular functions due to its localization. Moreover,
it may play a role in animal growth/development and metabolic state, although additional studies are
necessary to clarify the detailed mechanism(s) of action.