Gestational diabetes mellitus is associated with decreased adipose and placenta peroxisome proliferator-activator receptor γ expression in a Chinese population

Abstract

Peroxisome proliferator-activated receptors γ (PPARγ) is a member of nuclear receptor superfamily, and studies have demonstrated that dysregulation of PPARγ was associated with gestational diabetes mellitus (GDM), which is one of the most common metabolic abnormalities occurring during pregnancy. However, the results regarding the associations between PPARγ and GDM were conflicting among different studies. The present study aimed to determine the expression of PPARγ in adipose and placenta from GDM women in a Chinese population and to further explore the role of PPARγ in GDM women. The adipose and placenta tissues were isolated from GDM women and healthy pregnant women at term. The mRNA and protein expressions of PPARγ in adipose and placenta tissues were determined by qRT-PCR and western blot, respectively. Univariate correlation analysis was used to analyze the relationship between PPARγ expression and clinical characteristics of patients. The levels of tryglycerides and HbA1c were significantly higher, while the levels of low density lipoprotein (LDL) cholesterol, adiponectin and insulin were significantly lower in the GDM women than that in the healthy pregnant women. The mRNA and protein expression of PPARγ in both adipose and placenta from GDM women were significantly lower than that from healthy pregnant women. PPARγ mRNA expression in both adipose and placenta positively correlated with LDL cholesterol and adiponectin levels, and negatively correlated with tryglycerides and glucose levels at 0 h, 1 h and 2 h of 75 g oral glucose tolerance test. In summary, our results suggest that PPARγ may be a key modulator in the development of GDM, due to the roles of PPARγ in glucose homeostasis and adipose tissue development and function.

Adipose tissue function in healthy pregnancy, gestational diabetes mellitus and pre-eclampsia

“…Women with GDM had larger VAT adipocytes than normal glucose tolerant (NGT) controls and adipocyte size correlated with plasma glucose levels [ 58 ]. SAT expression of PPARγ was reduced in GDM compared to NGT controls [ 33 , 43 , 59 ] but others have found no differences in SAT or VAT PPARγ mRNA expression between GDM and NGT. Third trimester SAT and VAT expression of genes involved in adipocyte fatty acid uptake were decreased in GDM women compared to NGT women of similar BMI [ 33 ].…”

PPARs and Metabolic Disorders Associated with Challenged Adipose Tissue Plasticity

“…PPARγ is downregulated in the placenta in human patients with GDM. PPARγ has anti-inflammatory effects in the placenta and modulates embryogenesis, implantation, trophoblast invasion, and maternal spiral artery transformation [ 76 ]. Moreover, it has been demonstrated that reduced expression of PPARγ in placental tissues and serum is contributing to the development of preeclampsia, a specific pregnancy disorder in humans that contributes to maternal mortality [ 77 ].…”

Molecular mechanisms of insulin resistance in normal pregnancy and gestational diabetes

“…Вчені виявили зниження вмісту мРНК PPAR-γ та саме цього фактору на 40-50% в жировій тканині черевної порожнини вагітних із ожирінням і вагітних із ожирінням та ГЦД, порівняно з невагітними пацієнтками з ожирінням [43]. Одним із факторів, який може пригнічувати PPAR-γ під час вагітності, є прозапальний цитокін TNF-α [8].…”