Adiponectin isoform distribution in women: relationship to female sex steroids and insulin sensitivity

Abstract

Little is known about the associations between adiponectin and its oligomeric isoforms with female sex steroids, and the relevance of these relationships to insulin sensitivity in women. In a cross-sectional study of 32 healthy women (12 premenopausal, 10 postmenopausal, and 10 early pregnant), we investigated the correlations of total adiponectin and the high–, medium–, and low–molecular weight oligomers (HMW, MMW, and LMW, respectively) with estrogen, progesterone, adiposity, and insulin resistance. Fat mass and serum concentrations of estradiol, progesterone, insulin, glucose, and total and isoform adiponectin were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Serum concentrations of total and HMW adiponectin were highest in postmenopausal women and lowest in pregnant women. Concentrations of the MMW and LMW isoforms were not significantly different between the 3 groups. Total adiponectin, HMW adiponectin, and MMW adiponectin were negatively associated with estradiol and progesterone; but no associations between the LMW isoform and female sex steroids were observed. Fat mass and HOMA-IR were highest in pregnant women and lowest in premenopausal women. The HOMA-IR was positively associated with fat mass, estradiol, and progesterone, and negatively associated with total, HMW, and MMW adiponectin. Multivariate stepwise regression analysis revealed that fat mass explained 34% of the variance in HOMA-IR and that total and isoform adiponectin contributed an additional 10% to 15%. In the multivariate linear regression analysis, there were significant interactions of estradiol and progesterone with adiponectin or fat mass in the associations with HOMA-IR. In conclusion, there are strong negative associations of serum adiponectin and some of its isoforms with estradiol and progesterone. Female sex steroids are likely to affect insulin sensitivity through modulation of adiponectin and body fat.