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Comparison between Periprostatic adipose tissue and abdominopelvic adipose tissue

ABSTRACT: White adipose tissue accumulates at various sites throughout the body and some adipose tissue depots exist in close proximity to organs, whose function they could influence in a paracrine manner. Prostate gland is surrounded by a poorly characterized adipose depot called periprostatic adipose tissue (PPAT) playing emerging roles in prostate-related disorders. Unlike all other adipose depots, PPAT secretes pro-inflammatory cytokines even in lean individuals and does not increase in volume during obesity. These unique features remain unexplained due to the poor structural and functional characterization of this tissue. We characterized the structural organization of PPAT in patients in comparison to abdominopelvic adipose tissue (APAT), an extraperitoneal adipose depot whose accumulation is correlated to BMI. Unbiased comparisons of PPAT and APAT transcriptomes found that most differentially expressed genes were related to the hypoxia response. This chronic hypoxic state was associated with inflammation and fibrosis, which explain the failure of PPAT to expand in obesity and open new mechanistic avenues to explain its role in prostate-related disorders including cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196442 | GEO | 2022/03/11

REPOSITORIES: GEO

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Project description:Prostate cancer (PCa) is the second most prevalent malignancy in Western countries and the fifth leading cause of cancer-related death in men. The risk factors for PCa include obesity, age, and family history. Visceral fat has been linked to PCa risk, which has prompted researchers to investigate the influence of body composition and fat distribution on PCa prognosis. This study investigated the correlation between the composition of pelvic adipose tissue (PAT) and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, we prepared a periprostatic adipose tissue (PPAT)-conditioned medium (CM) to determine the influence of the PPAT secretome on the pathophysiology of PCa. This study included 60 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, and magnetic resonance imaging scans were analyzed, and body compositions were calculated to identify the correlations between adipose tissue volume and clinical PCa aggressiveness. CM was prepared using PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its influence was investigated using the PCa cell lines C4-2 and LNCaP and the prostate epithelial cell line PZ-HPV-7. Cell proliferation assays and RNA sequencing were performed. The initial prostate-specific antigen level was significantly correlated with pelvic and perirectal adipose tissue volumes. PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cells proliferated was significantly slower when cultured in PPAT-CM compared with when cultured in control- and PVAT-CM. RNA sequencing revealed that immune responses and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells. The cytokines or other secreted factors in PPAT-CM induced PCa cell apoptosis. This in vitro study revealed that the PPAT secretome inhibits PCa cells proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.

Project description:*Background: Adipocytes mainly function as energy storage and endocrine cells. The amount and distribution of fat are important factor that influence the meat quality in the beef industry. Fat depot can be found around internal organ (ometal), beneath the skin (subcutaneous), and between muscles (intramuscular). Different adipose depot showed the biological and genetic difference depending on their location. This inter-depot variation might be influenced by the inherent genetic programing for development of adipose depots. In this study, we used RNA-seq data to investigate the difference in transcriptome of various adipose depots in Hanwoo. *Results: Using RNA-seq, we identified 5797, 2156, and 5455 DEGs in the comparison between OI, OS, and IS respectively (FDR<0.01) and found 853, 48, and 979 DEGs specific to subcutaneous, intramuscular and omental fat respectively. DEGs in intramuscular fat were highly enriched the metabolism related pathways compared to other fat depots. DEGs specific to the omental fat is significantly enriched in PPAR signaling pathway and cell-junction related pathway. In subcutaneous fat, cytokine-cytokine receptor interaction with chemokines (CXC and CC subfamily) was the most significantly enriched the pathways. Interestingly, melanogenesis pathway was associated with the subcutaneous depot. Even though the adipose tissues shared the same pathways for adipocyte differentiation, the regulation of genes were different based on the depot. *Conclusions: We comparatively analyzed the transcripome profile from different adipose tissues using NGS and identified DEGs between adipose depot and specific to depot in Hanwoo animals. The functional annotation analysis of DEGs found that transcriptome profile difference in various adipose tissue of intramuscular, subcutaneous, and ometal fat. whole mRNA sequencing profiles of nine Korean native cattle (nine profiles of omental fat tissue, nine profiles of intramuscular fat tissue, nine profiles of subcutaneous fat tissue and eight profiles of muscle tissue)

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Comparison between Periprostatic adipose tissue and abdominopelvic adipose tissue

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