This study by Klöting et al. tested the hypothesis that mRNA expression of fat mass and obesity associated gene (FTO) and retinitis pigmentosa GTPase regulator interacting protein 1-like (RPGRIP1L) in visceral and subcutaneous adipose tissue is linked to obesity. They also investigated whether the FTO obesity risk alleles might explain variability in FTO and RPGRIP1L mRNA expression. Paired samples of visceral and subcutaneous adipose tissue were obtained from 55 Europid men (n=26) and women (n=29) who underwent open abdominal surgery for elective cholecystectomy or explorative laparotomy. Analysis of 55 paired samples of visceral and subcutaneous adipose tissue from 26 men and 29 women revealed 3-fold higher FTO mRNA levels in subcutaneous than in visceral adipose tissue, while RPGRIP1L mRNA expression was 1.6-fold higher in visceral than in subcutaneous adipose tissue. Moreover, subcutaneous and visceral FTO mRNA expressions were significantly correlated, and both depots correlated with age and were negatively correlated to body mass index and percent body fat. No significant relationship was found between both subcutaneous and visceral FTO expressions and fasting plasma glucose concentrations, HbA1c, and parameters of insulin sensitivity, including fasting plasma insulin concentrations and glucose uptake. However, no correlation between RPGRIP1L mRNA expression and anthropometric and metabolic parameters was seen in either fat depot. Expression of adipose tissue FTO mRNA is therefore fat depot-specific and correlates negatively with body mass index and total body fat.