Obesity and psychosocial stress influence the remodelling of pericardial adipose tissue

In obesity, fat is deposited at different sites around the body, but pericardial fat has been shown to have a particularly negative impact on the heart. Very little is known about the function of pericardial fat and how its phenotype is influenced by obesity. The aim of this study was to determine how obesity and stress affects the pericardial phenotype relative to visceral adipose tissue. Here we have used the obese Zucker rat (fa/fa) model induced by a mutation in the leptin receptor. Zucker rats develop hyperphagia with reduced energy expenditure, resulting in morbid obesity; impaired glucose and insulin sensitivity in a few weeks after birth. At 9 weeks of age lean (LZR) and obese (OZR) Zucker male rats were treated with or without unpredictable chronic mild stress (UCMS) for 8 weeks to mimic human clinical stress and depression. Adipose tissue can expand either through cellular hypertrophy or hyperplasia, with the former correlating with decreased metabolic health in obesity. To determine the phenotype for pericardial and visceral adipose tissue, tissue cellularity and gene expression were analysed. Tissue cellularity was determined following Haematoxylin and Eosin (H&E) staining, whilst qPCR was used to examine gene expression. Data from these experiments showed that, as expected, the OZR group were considerably heavier than the lean controls (LZR). Total plasma corticosterone and glucose all increased in the obese group indicating that obesity in itself increases stress. Furthermore, UCMS stress conditions had an additive effect by increasing these parameters further in both the lean LZR and the obese OZR group indicating that stress had a negative metabolic impact. H&E staining showed that there was greater heterogeneity in the cellularity of pericardial adipocytes compared with visceral adipose tissue, suggesting a mix of white, beige and brown‐like adipocytes. Analysis of tissue cellularity showed that obesity did not result in a significant alteration in adipocyte cell size in pericardial fat. However, when UCMS was combined with obesity there was a significant increase in adipocyte cell size relative to the lean group. This suggests that under non‐stressful conditions, pericardial adipose tissue does not expand predominantly through hypertrophy, unlike visceral adipocytes. However, stressful conditions combine with obesity to produce a more pathological pericardial adipose tissue phenotype. Gene expression analysis showed that UCMS stress caused an upregulation of leptin in the lean compared with the obese group. This suggests that leptin signalling is important for the stress‐dependent increase in adipose tissue leptin expression. Finally, the thermogenic marker UCP1 was upregulated in pericardial adipose tissue of obese rats relative to the lean controls but not in visceral tissue. These data strongly indicate that there is differential regulation of gene expression between pericardial and visceral adipose tissue which may have major implications for the heart in obesity. Support or Funding Information University of Reading, UK and the Petroleum Technology Development Fund, Nigeria