The Effects of HER2 Receptor Signaling on Human Brown Fat Activity

The objective of this observational study is to investigate the significance of the HER2 receptor for brown fat activity in humans. Our preliminary data clearly demonstrates that the ErbB signaling pathway, which includes the HER2 receptor, strongly promotes development and function of cultured human BAT cells. The HER2 receptor is a part of the ErbB signaling pathway, and antibodies against thee HER2 receptor are a part of the standard treatment for HER2-positive breast cancer. Therefore, the hypothesis is that the activity of brown fat will be reduced in patients treated with HER2 blocking antibody compared to patients who are not treated with HER2 blocking antibody. The present study simply takes advantage of the treatment protocol to explore the contribution of the HER2 receptor in the development of brown adipose tissue in humans. Participants will complete two testing days, one before and one after their treatment period of approx. one year. On the testing days, identification of brown fat activity will be performed using cooling and infrared thermography. In addition, resting metabolic rate and a glucose tolerance test will be performed. Since presence of active brown adipose tissue in humans is inversely related to obesity, total and visceral fat mass, plasma glucose levels, presence of cardiovascular disease and diabetes status, it is of great importance to investigate the molecular mechanisms for development of brown fat tissue and may lead to discovery of novel strategies to counteract obesity and obesity related disorders.