White Adipose Tissue Production and Release of IL-6 and TNF-α Do Not Parallel Circulating and Cerebrospinal Fluid Concentrations in Pregnant Rats

Abstract

IL-6 and TNF-alpha are synthesized in white adipose tissue both by adipocytes and by the stroma-vascular fraction. They both are known to interfere with insulin signaling, reducing insulin sensitivity and lipid deposition. At a central level, IL-6 enhances sympathetic nervous system activity, thus enhancing lipolysis and reducing fat mass. During late pregnancy, white adipose tissue (WAT) mass increases and insulin sensitivity decreases. To assess the involvement of both adipokines in such processes, we analyzed the tissue content and release of both adipokines in parametrial and subcutaneous WAT depots and their circulating and cerebrospinal fluid concentrations in nonpregnant rats and in pregnant rats by days 8, 15, and 19 of pregnancy. The tissue content of both adipokines was enhanced 5-6 times by day 8 until the end of pregnancy in parametrial WAT, whereas the increase took place by day 15-19 in subcutaneous WAT. No increase in tissue release was detected, suggesting a local action. However, circulating IL-6 concentration was enhanced by day 8 until the end of pregnancy, suggesting sources other than WAT. IL-6 concentration in cerebrospinal fluid paralleled the increases in serum by days 8 and 15, suggesting a systemic origin. However, it returned to basal levels by day 19, suggesting a central control for IL-6 entrance. TNF-alpha was not detected in either serum or cerebrospinal fluid. These results led us to conclude that across pregnancy adipokines control WAT depots in a time- and depot-dependent manner. They do so directly, by local production, but the enhanced concentrations of both circulating and CSF IL-6 suggest an indirect action mediated by the nervous system.