Cross Talk between Adipose Tissue and Placenta in Obese and Gestational Diabetes Mellitus Pregnancies via Exosomes

Abstract

Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR). Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM). Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body’s major energy reservoir. The role of adipose tissue, however, is not restricted to a “bag of fat.” The adipose tissue is an endocrine organ, secreting various adipokines, enzymes, growth factors, and hormones that take part in glucose and lipid metabolism. In obesity, the greater portion of the adipose tissue comprises fat, and there is increased pro-inflammatory cytokine secretion, macrophage infiltration, and reduced insulin sensitivity. Obesity contributes to systemic IR and its associated metabolic complications. Similar to adipose tissue, the placenta is also an endocrine organ. During pregnancy, the placenta secretes various molecules to maintain pregnancy physiology. In addition, the placenta plays an important role in metabolism and exchange of nutrients between mother and fetus. Inflammation at the placenta may contribute to the severity of maternal IR and her likelihood of developing GDM and may also mediate the adverse consequences of obesity and GDM on the fetus. Interestingly, studies on maternal insulin sensitivity and secretion of placental hormones have not shown a positive correlation between these phenomena. Recently, a great interest in the field of extracellular vesicles (EVs) has been observed in the literature. EVs are produced by a wide range of cells and are present in all biological fluids. EVs are involved in cell-to-cell communication. Recent evidence points to an association between adipose tissue-derived EVs and metabolic syndrome in obesity. In this review, we will discuss the changes in human placenta and adipose tissue in GDM and obesity and summarize the findings regarding the role of adipose tissue and placenta-derived EVs, with an emphasis on exosomes in obesity, and the contribution of obesity to the development of GDM.

Quantitative Proteomics by SWATH‐MS Suggest an Association Between Circulating Exosomes and Maternal Metabolic Changes in Gestational Diabetes Mellitus

“…Interestingly, we found an enrichment in proteins associated with adipocytes and macrophages but depletion of proteins associated with preadipocytes. Exaggerated adipose tissue dysfunction including hypertrophic expansion and chronic inflammation have been reported in insulin resistance . Inflammation leads to macrophage infiltration in adipose tissue leading to an inability to generate adipocytes and increased storage of lipids.…”

“…Inflammation leads to macrophage infiltration in adipose tissue leading to an inability to generate adipocytes and increased storage of lipids. Ultimately, this leads to dysfunctional and necrotic adipocytes characterized by increased adipocytokine release and reduced insulin sensitivity. Based on this, the increased number of proteins associated with adipocytes and macrophages in GDM exosomes may reflect the compromised function of adipose tissue.…”

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors

“…A number of publications have addressed placental EVs and their potential role in pregnancy and its complications . Several ex vivo (eg, placental perfusion) and in vivo systems have been used as a source of EVs.…”

Extracellular vesicles in normal pregnancy and pregnancy‐related diseases

“…Metabolism dysregulation is closely related to some pregnant complications, for instance, GDM and foetal overgrowth . Compared to AT exosomes of NGT controls, AT exosomes of GDM could increase the expression of genes associated with glycolysis and glycogenolysis in placental cells.…”