Effect of a combined estrogen and progesterone oral contraceptive on circulating adipocytokines adiponectin, resistin and DLK-1 in normal and obese female rhesus monkeys

Abstract

Background: Hormonal contraception is the most common medication used by reproductive aged women but there is little understanding of the impact of hormonal contraception on obesity and metabolism. Adipokine levels (adiponectin, resistin) and markers of adipocyte development (DLK-1) are altered in obese animals and humans and are associated with increased cardiovascular risk. We sought to determine the effect of combined hormonal oral contraceptive pills (COCs) on circulating adiponectin, resistin and DLK-1 levels in obese and normal-weight rhesus macaque monkeys.

Methods: Serum adiponectin, resistin and DLK-1 levels in reproductive-age female rhesus macaques of normal (n = 5, mean = 5.76 kg) and inherently obese (n = 5, mean = 8.11 kg) weight were determined before, during and 2 months after cessation of 8 months of continuous treatment with COCs.

Results: The obese group alone showed a significant decrease (p<.01) in weight with COC use, which returned to baseline after COC cessation. Baseline adiponectin levels prior to COC treatment were lower in the obese group (p<.05). Adiponectin levels increased from baseline in both groups, but more so in the obese group (p<.05). Resistin levels were similar at baseline, with an increase in both groups following treatment. Circulating resistin remained elevated above baseline levels after COC cessation, particularly in the obese group (p<.05). While DLK-1 levels did not change significantly in either group, a trend for higher levels in obese animals was observed.

Conclusions: COC use may alter metabolic processes via direct (resistin) or indirect (adiponectin) means, while unchanging DLK1 levels suggest they do not affect adipocyte development. COCs may directly increase resistin levels, as observed in both groups. As adiponectin is inversely related to adipocyte mass, increased levels in the obese group are likely attributed to weight loss.

Fig. 1

Serum adiponectin levels of individual normal weight (A) or obese (B) monkeys prior to (baseline), during (2 and 6 months), and following (2 months) COC treatment. Each line represents an individual animal through the course of the study interval.

Fig. 2

Mean serum adiponectin levels over time in obese and normal weight rhesus macaque monkeys on COCs. Significance (p<.05) is indicated for comparisons between groups at each time-point (brackets) and the change from baseline levels within each group (*). Error bars signify SD.

Fig. 3

Mean serum resistin levels in obese and normal weight rhesus macaque on COCs. Significance (p<.05) is noted for a change from baseline levels within each group (*). No significant differences were observed between groups at each time-point. Error bars signify SD.

Fig. 4

Mean serum DLK-1 levels in obese and normal weight rhesus macaque on COCs. No significant differences exist between groups at each time-point or from baseline levels within each group. Error bars signify SD.