Pattern Specification and Immune Response Transcriptional Signatures of Pericardial and Subcutaneous Adipose Tissue

Abstract

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Recent studies suggest that pericardial adipose tissue (PCAT) secretes inflammatory factors that contribute to the development of CVD. To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between PCAT and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. As it was unknown whether PCAT-secreted factors are produced by adipocytes or cells in the supporting stromal fraction, we also sought to identify differentially expressed genes in isolated pericardial adipocytes vs. isolated subcutaneous adipocytes. Using microarray analysis, we found that: 1) pericardial adipose tissue and isolated pericardial adipocytes both overexpress atherosclerosis-promoting chemokines and 2) pericardial and subcutaneous fat depots, as well as isolated pericardial adipocytes and subcutaneous adipocytes, express specific patterns of homeobox genes. In contrast, a core set of lipid processing genes showed no significant overlap with differentially expressed transcripts. These depot-specific homeobox signatures and transcriptional profiles strongly suggest different functional roles for the pericardial and subcutaneous adipose depots. Further characterization of these inter-depot differences should be a research priority.

Quantifying Size and Number of Adipocytes in Adipose Tissue

“…This difference coincides with a divergence in the expression of genes associated with glucose intolerance (increased Glut4 , decreased insulin receptor (Lefebvre et al, 1998)) and atherosclerosis (increased CCL4 , CCL5 , and IL-1β ) (Lau et al, 2011). Unexpectedly, we have also observed differences in gene expression across a WAT depot.…”

“…As was mentioned above, significant differences exist between the expression profile of adipocyte genes between tissues and within tissues (Brochu et al, 2001; Fujimoto et al, 1999; Kloting et al, 2010; Lau et al, 2011; Lefebvre et al, 1998; Nicklas et al, 2004). Analysis of adipocyte size using our described method has indicated that there are differences in the distribution of adipocyte sizes and average area between inguinal and epididymal WAT (Fig.…”

“…It is well established that increased visceral adipose tissue is highly associated with obesity-related cardiovascular and metabolic abnormalities when compared to subcutaneous depots (Brochu et al, 2001; Fujimoto et al, 1999; Kloting et al, 2010; Lau et al, 2011; Lefebvre et al, 1998; Nicklas et al, 2004). This difference coincides with a divergence in the expression of genes associated with glucose intolerance (increased Glut4 , decreased insulin receptor (Lefebvre et al, 1998)) and atherosclerosis (increased CCL4 , CCL5 , and IL-1β ) (Lau et al, 2011).…”

Heterogeneity of adipose tissue in development and metabolic function

“…Table 2 provides an overview of developmental genes that are differentially expressed among adipose tissue depots in rodents and humans. Most notably, in humans, a set of homeobox-type transcription factors was identified to be differentially regulated between SAT and VAT (HOXC9, HOXC10, HOXA9, HOXA10, HOXC6, HOXB7 and PAX3) (Brune et al, 2016;Lau et al, 2011;Vohl et al, 2004), as well as between different SAT depots. HOXA2, HOXA3, HOXA4, HOXA5, HOXA9, HOXB7, HOXB8, HOXC8 and IRX2 are downregulated in both adipocytes and stromal vascular cells of the gluteal subcutaneous compared with the abdominal subcutaneous depot.…”

Leptin‐dependent differential remodeling of visceral and pericardial adipose tissue following chronic exercise and psychosocial stress

“…16 In addition, the transcriptome of PAT from patients with CAD revealed an upregulation of genes involved in immune and inflammatory processes. 14,17 Exercise training has shown numerous beneficial effects on adipose tissue health in rodents 18 and humans. 19 In well-conditioned athletes, the mass of adipose tissue accounts for 2% to 3% of body weight, suggesting the beneficial role of exercise in reducing fat mass.…”