Characterization of abdominal adiposity and its relationship to adipokines and the adaptive immune response

Abstract

A large body of evidence demonstrates that obese pregnant women have a greater risk of pregnancy and delivery complications and poorer health outcomes compared with normal weight pregnant women. Most research on the impact of obesity in pregnancy defines obesity by body mass index (BMI), a measurement that does not consider the location of body fat. Abdominal fat mass is associated with cardiometabolic diseases so it is reasonable to postulate that it plays a greater role in obesity-related pregnancy complications, yet the role of abdominal fat in pregnancy is not well defined. It is known that obese pregnant women have higher circulating interleukin 6, C-reactive protein, and higher macrophage expression in the placenta. It is also known that T cell populations increase in non-pregnant obese individuals. However, it is not known how T cells respond to the incidence of obesity in pregnancy. The main purpose of this research is to examine the relationships between abdominal fat mass and circulating adipokines and peripheral CD4+ T cells in pregnancy. We recruited thirty-eight women from the University of Kansas Obstetrics and Gynecology Clinic in their third trimester for the Pregnancy Health Study. Recruitment was focused on women in healthy pregnancy and with respect to a full spectrum of pre-pregnancy BMI (18.5 - 40). Before delivery, blood was collected to measure circulating adipokines by ELISA and measure CD4+ T cell cytokine production by multiplex. CD4+ T cells were isolated from peripheral blood mononuclear cells by positive selection and stimulated ex vivo to examine cytokine production. Total body fat was measured by dual x-ray energy absorptiometry in the subjects within three-weeks postpartum. At the same visit, magnetic resonance imaging scans on the abdominal region occurred in a subset of twenty subjects. ImageJ was used to quantify abdominal subcutaneous and visceral fat mass from the axial images. Women categorized as overweight or obese by BMI had significantly greater amounts of abdominal subcutaneous and visceral fat mass compared to normal-weight BMI women, as well as greater total body fat. We found a strong relationship between abdominal visceral fat mass and resistin but no other adipokines measured (leptin, visfatin, and adiponectin) correlated with abdominal visceral fat mass. No relationships were observed between abdominal subcutaneous fat mass and any adipokine. Leptin was the only adipokine to correlate with total body fat and pre-pregnancy BMI. Additionally, there were no correlations between pre-pregnancy BMI, total body fat (with one exception), or abdominal subcutaneous fat with CD4+ T cell production of cytokines. We did observe a significant decrease in cytokine concentration in relationship to abdominal visceral adiposity. This dampening effect was observed across all categories of CD4+ T cell cytokines. Together, these results suggest that visceral fat mass in pregnancy has the potential to play a role in obesity-related pregnancy complications whereas BMI is a poor indicator of the effect of fat on adaptive immunity. Even though women with an overweight or obese pre-pregnancy BMI have greater amounts of abdominal fat mass, BMI was unrelated to physiologically relevant adipokines (leptin as the exception) and CD4+ T cell cytokines. Visceral fat is an ectopic fat compartment and should be studied as a physiologically relevant factor in obesity-related pregnancy complications, regardless of a woman's weight status.