Developmental programming: Transcriptional regulation of visceral and subcutaneous adipose by prenatal bisphenol-A in female sheep

Abstract

Background: Bisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood.Objective: To determine the impact of prenatal BPA exposure on the transcriptome of VAT and SAT adipose depots. Methods: RNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Differences in transcriptional profiling of SAT and VAT in controls and the effect of prenatal BPA treatment on individual genes and gene pathways were determined.Results: There were 179 differentially expressed genes (p adjusted <0.05, log 2 -fold change >2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. In SAT, BPAtreatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated).In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways. Conclusion:Prenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep.

New Evidence on BPA’s Role in Adipose Tissue Development of Proinflammatory Processes and Its Relationship with Obesity

“…However, other studies showed different results regarding the behavior of subcutaneous adipose tissue in the presence of BPA. Another study, evaluating sheep exposed to BPA with daily doses of 0.5 mg/kg during their fetal growth, demonstrated development of visceral adipose tissue hypertrophy at 21 months after birth [81]. This treatment allowed free BPA concentrations of 2.62 ± 0.52 ng/mL collected from the umbilical artery on day 90 of fetal life with values within the range observed in human umbilical cord blood concentrations at mid-gestation [27].…”

“…In addition, differential gene expression was evaluated by tissue type (subcutaneous vs. visceral) and by treatment (control vs. prenatal BPA group). The results showed, when tissue type was compared, a positive regulation of inflammation, oxidative stress, and adipose differentiation genes in subcutaneous adipose tissue compared to in visceral adipose tissue [81]. However, when comparing subcutaneous tissue gene expression for each treatment (control vs. BPA treatment), BPA downregulated several genes involved in immune cell pathways, including those involved in leukocyte activation, inflammatory response, and cytokine production.…”

Transcriptional Features of Cattle Visceral and Subcutaneous Adipose Tissues: A Study of RNA-seq

“…Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are the two major types of adipose tissue, according to their distribution in mammals [4]. There are many differences between VAT and SAT including anatomical, cellular, molecular, physiological, clinical, and prognostic [5]. Fat storage and allocation within body depots of farm animals are associated with animal health and meat quality, these differences are caused by a variety of mechanisms such as a different content of immune cells, different sensitivity to lipolytic and antilipolytic stimulation, and different metabolic activities [6] [7].…”