Differential Expression of FXR and Genes Involved in Inflammation and lipid Metabolism Indicate Adipose Tissue Dysfunction in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent metabolic alteration in pregnancy. Several abnormalities in visceral adipose tissue (VAT) have been described as part of its pathophysiology including hypertrophy, inflammation and altered lipid metabolism. Farnesoid X receptor (FXR) is involved in adipocyte physiology and inflammation, so its expression may correlate with the expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lipoprotein lipase (LPL), and two fatty acid transporters (SLC27A2, and SLC27A4). AIM: To compare the FXR, LPL, SLC27A2, SLC27A4, TNF-α, and IL-10 mRNA expression in VAT between women with GDM and healthy pregnant (HP) women. Secondarily, to evaluate the potential correlation between these expression levels. MATERIALS AND METHODS: Cross-sectional study of 50 GDM and 50 HP women. Conventional biochemical tests were performed and relative mRNA expression in VAT was measured by RT-qPCR. RESULTS: Gene expression levels of FXR and IL-10 were lower, whereas those of LPL, as well as the TNF-α/IL-10 ratio, were higher in women with GDM compared to HP. Pre-pregnancy BMI was the main significant independent variable for FXR levels in VAT from women with GDM. In all women, LPL expression levels correlated positively with those of SLC27A2. Only in women with GDM, IL-10 expression levels correlated negatively with those of SLC27A2, and SLC27A4. CONCLUSIONS: GDM is associated with decreased expression of FXR and IL-10 and increased expression of LPL, as well as a higher TNF/IL-10 ratio in VAT. These results suggest increased lipid storage and pro-inflammatory state indicating VAT dysfunction in this metabolic disorder.

New Insights into Adipokines in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy and has considerable short- and long-term consequences for the health of both the mother and the newborn. Within its pathophysiology, genetic, nutritional, epigenetic, immunological, and hormonal components have been described. Within the last two items, it is known that different hormones and cytokines secreted by adipose tissue, known collectively as adipokines, are involved in the metabolic alterations underlying GDM. Although the maternal circulating profile of adipokines in GDM has been extensively studied, and there are excellent reviews on the subject, it is in recent years that more progress has been made in the study of their expression in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), placenta, and their concentrations in the umbilical circulation. Thus, this review compiles and organizes the most recent findings on the maternal and umbilical circulating profile and the levels of expression of adipokines in VAT, SAT, and placenta in GDM.

Alteración del perfil materno de adipocinas circulantes en preeclampsia / Altered maternal adipokine profile in preeclampsia

Resumen OBJETIVOS: Evaluar las concentraciones séricas maternas de las adipocinas: adiponectina, adipsina, leptina, lipocalina-2, proteína quimioatrayente de monocitos-1, factor de crecimiento nervioso, resistina y factor de necrosis tumoral alfa y su relación con el índice de masa corporal previo al embarazo y la ganancia de peso gestacional en mujeres con preeclampsia comparadas con mujeres sanas, y hacer un análisis de la clasificación de preeclampsia en temprana y tardía. MATERIALES Y MÉTODOS: Estudio transversal, comparativo, retrolectivo, con muestreo no probabilístico por conveniencia efectuado en pacientes atendidas en el Hospital de Gineco-Obstetricia 3, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS). En el preoperatorio se tomó una muestra de sangre para determinar las concentraciones séricas de las adipocinas mediante ensayos multianalito. RESULTADOS: Se estudió una muestra de 75 mujeres con embarazo sano y 44 con preeclampsia (temprana n = 20, tardía n = 24). Solo las concentraciones de adipsina, leptina y factor de necrosis tumoral alfa fueron mayores en preeclampsia que en el embarazo sano [mediana (rango intercuartílico): 3.9 µg/mL (2.9-5.4) vs 2.5 µg/mL (1.9-3.1), 10.6 ng/mL (6.0-19.1) en comparación con 7.1 ng/mL (3.8-12.4), 3.6 pg/mL (2.7-5.8) vs 2.9 (2.3-3.5), respectivamente]. Las concentraciones de las adipocinas no se correlacionaron con el índice de masa corporal previo al embarazo ni con la ganancia de peso gestacional. No hubo diferencias significativas en las concentraciones entre los subtipos de preeclampsia. CONCLUSIÓN: En el tercer trimestre del embarazo la preeclampsia se asocia con un perfil sérico de adipocinas alterado, caracterizado por concentraciones elevadas de adipsina, leptina y factor de necrosis tumoral alfa, que no se relaciona con el índice de masa corporal previo al embarazo, la ganancia de peso gestacional y el subtipo de preeclampsia.

Abstract OBJECTIVES: To evaluate maternal serum concentrations of adipokines: adiponectin, adipsin, leptin, lipocalin-2, monocyte chemoattractant protein-1, nerve growth factor, resistin and tumor necrosis factor-alpha and their relationship with pre-pregnancy body mass index and gestational weight gain in women with preeclampsia compared with healthy women, and to perform an analysis classifying preeclampsia as early and late. MATERIALS AND METHODS: Cross-sectional, comparative, retrolective, non-probabilistic convenience sampling study carried out in patients attended at the Hospital de Gineco-Obstetricia 3, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS). Preoperatively, a blood sample was taken to determine serum adipokine concentrations by multianalyte assays. RESULTS: A sample of 75 women with healthy pregnancy and 44 with preeclampsia (early n = 20, late n = 24) was studied. Only adipsin, leptin, and tumor necrosis factor-alpha concentrations were higher in preeclampsia than in healthy pregnancy [median (interquartile range): 3. 9 µg/mL (2.9-5.4) vs. 2.5 µg/mL (1.9-3.1), 10.6 ng/mL (6.0-19.1) compared to 7.1 ng/mL (3.8-12.4), 3.6 pg/mL (2.7-5.8) vs. 2.9 (2.3-3.5), respectively]. Adipokine concentrations did not correlate with pre-pregnancy body mass index and gestational weight gain. There were no significant differences in concentrations between preeclampsia subtypes. CONCLUSION: In the third trimester of pregnancy, preeclampsia is associated with an altered serum adipokine profile, characterized by elevated concentrations of adipsin, leptin, and tumor necrosis factor-alpha, which is not related to prepregnancy body mass index, gestational weight gain, and preeclampsia subtype.