Assessing adipose tissue depot differences in thermogenesis during early life in sheep and browning response in humans with pheochromocytoma

Obesity and associated comorbidities such as diabetes are currently major global health problems. It has been shown that individual sites or depots of fat have different properties and effects on whole body physiology. Of particular interest are depots that display thermogenic characteristics, known as brown or beige adipose tissue, which may be able to increase energy expenditure and clear excess glucose and lipids from the circulation. The aim of this thesis was to compare adipose tissue depots in terms of their capacity for thermogenesis in early life using sheep as an animal model and browning response to chronic adrenergic stress in humans with pheochromocytoma. Epicardial and paracardial adipose tissues were focused on in the sheep study as they have been described as thermogenic in some adult humans but these findings have been inconclusive. The characterisation of these depots and their capacity for thermogenesis in early life has not been established, especially in comparison to other known depots of white and brown adipose tissue. My results show that epicardial and paracardial adipose tissue have increased thermogenic gene expression and uncoupling protein 1 in comparison to omental white adipose tissue suggesting they may play a role in thermogenesis in early life. These depots undergo remodelling over the first 28 days changing from brown to white adipose tissue. In sheep, this adipose tissue transition occurs without evidence of apoptosis and which may suggest other cellular mechanisms are responsible for this process. The browning capacity of different fat depots is important for targeting therapeutic interventions. As a model of catecholamine excess, samples of human periadrenal and subcutaneous adipose tissue were collected from patients with pheochromocytoma as well as patients undergoing adrenalectomy for benign tumours (control group). The data suggests periadrenal adipose tissue can undergo browning in some patients with pheochromocytoma. These patients had the highest plasma catecholamine concentrations suggesting a possible threshold is required to elicit browning. Subcutaneous adipose tissue did not display signs of browning suggesting that this depot does not respond to chronic adrenergic stress. It may therefore have a lack of browning capacity compared to visceral depots. In conclusion, both studies suggest differences between adipose tissue depots in thermogenic capacity both in development in early life and capacity for browning in later life