Unique Genetic and Histological Signatures of Mouse Pericardial Adipose Tissue.

A Al-Dibouni,R Gaspar,S Boateng,R D Cox,S Ige,F R Cagampang,D Sellayah,J Gibbins

doi:10.3390/nu12061855

Abstract

Obesity is a major risk factor for a plethora of metabolic disturbances including diabetes and cardiovascular disease. Accumulating evidence is showing that there is an adipose tissue depot-dependent relationship with obesity-induced metabolic dysfunction. While some adipose depots, such as subcutaneous fat, are generally metabolically innocuous, others such as visceral fat, are directly deleterious. A lesser known visceral adipose depot is the pericardial adipose tissue depot. We therefore set out to examine its transcriptional and morphological signature under chow and high-fat fed conditions, in comparison with other adipose depots, using a mouse model. Our results revealed that under chow conditions pericardial adipose tissue has uncoupling-protein 1 gene expression levels which are significantly higher than classical subcutaneous and visceral adipose depots. We also observed that under high-fat diet conditions, the pericardial adipose depot exhibits greatly upregulated transcript levels of inflammatory cytokines. Our results collectively indicate, for the first time, that the pericardial adipose tissue possesses a unique transcriptional and histological signature which has features of both a beige (brown fat-like) but also pro-inflammatory depot, such as visceral fat. This unique profile may be involved in metabolic dysfunction associated with obesity.

Highlights

Obesity is a major risk factor for a plethora of metabolic disturbances and diseases, including heart disease, which is a leading cause of death in most industrialised countries [1]
For comparison of the transcriptional alterations occurring at baseline, markers associated with adipogenesis (Figure 2A–C), inflammation (Figure 2D–G), thermogenesis (Figure 2H–J) and mitochondrial function (Figure 2K–M) were assessed in gonadal white adipose tissue (gWAT), inguinal white adipose tissue (iWAT), intercapsular brown adipose tissue (iBAT) and pericardial adipose tissue (PAT), in 30-week-old male mice fed a standard chow diet
The ‘master regulators of adipogenesis’, peroxisome proliferator-activated receptor gamma (PPARγ) (Figure 2B) and CCAAT/enhancer binding protein (C/EBPα) (Figure 2C), exhibited a similar transcriptional profile, but only iBAT showed a significant reduction in PPARγ gene expression compared to iWAT (p < 0.05), with no other significant changes between the adipose tissue depots in these genes

Summary

Introduction

Obesity is a major risk factor for a plethora of metabolic disturbances and diseases, including heart disease, which is a leading cause of death in most industrialised countries [1]. Ectopic fat deposition, which may refer to accumulation of triglycerides beyond the adipose tissue or the presence of non-classical adipose tissue depots is commonly associated with increased cardiovascular risk and poorer clinical outcomes [2,3], with a number of genetic determinants of ectopic fat having been identified [4]. The classical adipose tissue depots can be classified into two major types: white adipose tissue (WAT) and brown adipose tissue (BAT), the latter of which is concerned with thermogenesis and lipolysis, while the former is associated with lipid storage [5,6]. Visceral WAT depots include intra-abdominal fat and gonadal fat, respectively. These depots are associated with metabolically deleterious hypertrophic adipose tissue growth and inflammation, Nutrients 2020, 12, 1855; doi:10.3390/nu12061855 www.mdpi.com/journal/nutrients

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Results

Conclusion