Differential remodelling of visceral and pericardial adipose tissue in response to stress and exercise

Abstract

Obesity is driven by an imbalance between caloric intake and energy expenditure, causing excessive storage of nutrients in adipose tissue at different sites around the body. Increased visceral adipose tissue (VAT) is associated with diabetes, whilst pericardial adipose tissue (PAT) is associated with cardiac pathology. Adipose tissue can expand either through cellular hypertrophy or hyperplasia, with the former correlating with decreased metabolic health in obesity. The aim of this study was to determine how VAT and PAT remodel in response to obesity, stress and exercise.Here we have used the obese Zucker rats which develop hyperphagia with reduced energy expenditure, resulting in morbid obesity as a result of leptin resistance. At 9 weeks of age lean (LZR) and obese (OZR) Zucker male rats were treated with or without unpredictable chronic mild stress or exercise for 8 weeks. To determine the phenotype for PAT and VAT, tissue cellularity and gene expression were analyzed. Tissue cellularity was determined following haematoxylin and eosin staining, whilst qPCR was used to examine gene expression.PAT adipocytes were significantly smaller than those from VAT and had a more biege‐like appearance. In the OZR group, VAT adipocyte cell size increased significantly compared with LZR, whilst PAT showed no change. Exercise and stress resulted in a significant reduction in VAT cellularity in OZR, whilst PAT showed no change. This suggests that PAT cellularity does not remodel significantly compared with VAT. Picro sirus red staining indicated that PAT had significantly more fibrosis than VAT. However, this fibrosis was decreased following stress treatment. This data indicate that the extracellular matrix of PAT is able to remodel more readily than in VAT.Gene expression analysis showed that PAT expressed higher levels of UCP1 compared with VAT, indicating that it has a more brown‐like phenotype. In the LZR group, exercise increased insulin receptor substrate 1 (IRS1) in PAT, but was decreased in the OZR group. On the other hand, in VAT, exercise decreased IRS1 in LZR, whilst increasing it in the OZR. This suggests that in obesity, VAT is more responsive to exercise and subsequently becomes less insulin resistant compared with PAT. In VAT, stress increased PPAR‐γ expression in the OZR group but decreased it in the PAT. This suggests that in obesity, stress increases adipogenesis more significantly in the VAT compared with PAT.Taken together, our data suggest that VAT is considerably more plastic than PAT and remodels rapidly in response to obesity, exercise and psychological stress.