Abstract/Summary

Introduction: The nutritional environment encountered in utero and during adulthood influences the development of adipose tissue (AT). Brown-like cells residing in AT that often promote a beneficial metabolic profile, may become dysfunctional in metabolic disease. Alterations in AT may increase the risk of developing Cardiovascular Disease and Type 2 Diabetes. Aim: There is still a lack of knowledge regarding the role of AT associated with the heart, such as pericardial adipose tissue (PAT), in normal and dysregulated metabolism. This thesis aims to provide an insight into the therapeutic potential and adipogenic, inflammatory and thermogenic capacity of PAT, in mice. Method: The transcriptional and histological profile of PAT, compared to other adipose depots, was assessed in male C57BL/6 mice. Firstly, PAT was harvested from mice fed either a chow or high-fat (HF)-diet, for 7 or 26 weeks. Secondly, PAT was sampled from offspring mice fed a post-weaning diet of either a chow or HF-diet for 26 weeks, from dams fed a chow or HF�diet prior to and during pregnancy and lactation. Finally, PAT was collected from chow and HF-fed mice treated orally with and without Compound 14 (Cpd14) for 10 days and after a 26- day recovery period. Results: Firstly, there were differences in brown and white adipocyte markers of PAT, depending on the nutritional environment encountered. Secondly, both the maternal and offspring diet influenced the thermogenic potential of PAT. Finally, Cpd14 potentially upregulated the thermogenic capacity of PAT to induce weight loss in obese mice. Conclusion: Collectively, PAT in mice has a unique transcriptional and histological profile, altered by dietary exposure in utero and during adulthood, and upon therapeutic stimulation. The underlying mechanisms involved are still unknown, however there is compelling evidence that PAT as a beige depot is an attractive therapeutic target.