In preeclampsia, maternal third trimester subcutaneous adipocyte lipolysis is more resistant to suppression by insulin than in healthy pregnancy

Obesity increases preeclampsia risk, and maternal dyslipidemia may result from exaggerated adipocyte lipolysis. We compared adipocyte function in preeclampsia with healthy pregnancy to establish whether there is increased lipolysis. Subcutaneous and visceral adipose tissue biopsies were collected at caesarean section from healthy (n=31) and preeclampsia (n=13) mothers. Lipolysis in response to isoproterenol (200 nmol/L) and insulin (10 nmol/L) was assessed. In healthy pregnancy, subcutaneous adipocytes had higher diameter than visceral adipocytes (<i>P</i><0.001). Subcutaneous and visceral adipocyte mean diameter in preeclampsia was similar to that in healthy pregnant controls, but cell distribution was shifted toward smaller cell diameter in preeclampsia. Total lipolysis rates under all conditions were lower in healthy visceral than subcutaneous adipocytes but did not differ after normalization for cell diameter. Visceral adipocyte insulin sensitivity was lower than subcutaneous in healthy pregnancy and inversely correlated with plasma triglyceride (<i>r</i>=−0.50; <i>P</i>=0.004). Visceral adipose tissue had lower <i>ADRB3, LPL,</i> and leptin and higher insulin receptor messenger RNA expression than subcutaneous adipose tissue. There was no difference in subcutaneous adipocyte lipolysis rates between preeclampsia and healthy controls, but subcutaneous adipocytes had lower sensitivity to insulin in preeclampsia, independent of cell diameter (<i>P</i><0.05). In preeclampsia, visceral adipose tissue had higher <i>LPL</i> messenger RNA expression than subcutaneous. In conclusion, in healthy pregnancy, the larger total mass of subcutaneous adipose tissue may release more fatty acids into the circulation than visceral adipose tissue. Reduced insulin suppression of subcutaneous adipocyte lipolysis may increase the burden of plasma fatty acids that the mother has to process in preeclampsia

Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancy

Obesity increases preeclampsia risk. Adipose tissue inflammation may contribute to the clinical syndrome of pre-eclampsia. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in pre-eclampsia and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and preeclampsia (n=13) mothers. Basal and lipopolysaccharide stimulated adipocyte TNFα, IL-6, CCL-2 and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined. In pre-eclampsia only, visceral adipose tissue TNFα release was increased after lipopolysaccharide stimulation (57 [76] vs 81 [97] pg/mL/ug DNA, p=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r=-0.61, p=0.030) in pre-eclampsia. Visceral adipocyte IL-6 release was increased after lipopolysaccharide stimulation in pre-eclampsia only (566 [696] vs 852 [914] pg/mL/ugDNA, p=0.019). Visceral adipocyte CCL-2 basal (67 [61] vs 187 [219] pg/mL/ugDNA, p=0.049) and stimulated (46 [46] vs 224 [271] pg/mL/ugDNA, p=0.003) release was greater than in subcutaneous adipocytes in pre-eclampsia only. In pre-eclampsia, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13-4.14] vs 0.8 [0.00-1.27] TNF / PPIA ratio, p=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] vs 51.0[29.9] CSF1R/PPIA ratio, p=0.011) and activated (cfms+) macrophage count (6.7[2.6] vs 15.2[8.8] % cfms+/adipocyte, p=0.031) were higher in pre-eclampsia than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in pre-eclampsia. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with pre-eclampsia

Short and long term strategies for the management of hypertensive disorders of pregnancy

The hypertensive disorders of pregnancy include gestational hypertension and preeclampsia, both de novo and superimposed on chronic hypertension. These disorders occur frequently among pregnant woman and are important contributors to maternal and perinatal mortality and morbidity worldwide. In this review, we will focus on recent developments in the prediction and pathogenesis of these disorders, prevention of preeclampsia and current strategies for the treatment of hypertension in pregnancy. We also explore the evidence relating adverse pregnancy outcome to an increased future risk of cardiovascular disease and potential strategies to minimize this risk