Oestrogen receptor alpha gene expression levels are reduced in obese compared to normal weight females.

To determine whether oestrogen receptor (ER)alpha messenger RNA (mRNA) levels or single nucleotide polymorphisms (SNPs) are associated with obesity in Swedish women. ERalpha mRNA expression levels were measured by real-time qPCR in subcutaneous adipose tissue from non-obese (N=16, BMI<30) and obese (N=17, BMI>or=30) women. In addition, ERalpha mRNA expression levels were determined in isolated adipocytes. ERalpha promoter usage was characterized by 5' RACE and by real-time qPCR in subcutaneous adipose tissue from the same non-obese and obese women. Two ERalpha SNPs were scored in 509 non-obese and 489 obese females. ERalpha mRNA expression levels were lower in obese compared to non-obese women in both subcutaneous adipose tissue and in adipocytes. We show that two ERalpha promoters are differentially utilized in obese and non-obese individuals. We did not find any significant association between obesity and the ERalpha SNPs or haplotypes assayed. The reduced ERalpha mRNA levels observed in adipose tissue from obese compared to non-obese women support a role for oestrogen signaling via ERalpha, in control of body weight. Mechanistic studies of the role of ERalpha in adipocytes and how its expression is regulated in relation to fat mass should be performed. The latter studies should focus on the two promoters that are used differently in obese and non-obese individuals.