Brown adipose tissue and cold acclimation
Upon mild cold exposure people can increase their energy expenditure. This is called non-shivering thermogenesis (NST). Moreover, during prolonged cold exposure NST can increase, this is called adaptive thermogenesis. This metabolic reaction is subject to high inter-individual variability. These differences might be explained by the amount of active brown adipose tissue (BAT). Furthermore, a negative correlation between BAT activity and BMI was found and obese people show an impaired cold-induced thermogenesis. In addition, diabetic status has been associated with reduced BAT activity independently of BMI. Recently, we showed that cold-acclimation had a major effect on insulin sensitivity in type 2 diabetic patients. Here we will examine the effect of 10 day cold acclimation on metabolic flexibility, cardiovascular function and postprandial insulin sensitivity in type 2 diabetic patients. Within the DMRG research group, we have the possibility to study human BAT function in vitro. This in vitro model provides opportunities to test novel compounds for their potential to activate human BAT. Furthermore this in vitro model for human BAT can be used to unravel molecular mechanisms important in human in vivo BAT function.
This project is financed by a grant from CVON
PhD student: Carlijn Remie, Michiel Moonen
Postdoc: Emmani Nascimento
BMP9 mediated effects on human brown adipose tissue adipogenesis and metabolism
Type 2 diabetes (T2D) is characterized by elevated blood glucose levels and insulin resistance. Brown adipose tissue (BAT) is a glucose utilizing tissue with high numbers of uncoupling protein 1 (UCP1) containing mitochondria that produce heat via mitochondrial uncoupling. The current finding that BAT is present in adult humans has raised interest in BAT, however its role in the etiology of T2D remains unclear.
Studies in rodent models have shown a prominent role for bone morphogenetic protein (BMP) in adipogenesis of BAT. Recently BMP9 has shown promise in adipogenesis of white adipose tissue (WAT). Earlier findings have indicated BMP9 as an important factor regulating glucose homeostasis. BMP9 together with BMP10 are specific in their mode of action which is mediated via activin like kinase. However it remains unclear how BMP9 can normalize glucose homeostasis via human BAT. We therefore hypothesize that increased adipogenesis of human BAT through BMP9 enhances BAT function, resulting in increased glucose uptake from the blood and thus in normalization of glucose homeostasis. We will utilize a unique in vitro human cell model for BAT in which adipose tissue derived stem cells from a BAT biopsy will be differentiated into mature adipocytes in the presence of BMP9. In the human BAT model we will examine insulin-stimulated glucose uptake and mitochondrial thermogenic capacity. These studies will reveal novel insights into the role of BMP9 in regulating glucose homeostasis and energy expenditure in human BAT by means of an in vitro system.
This project was financed by a grant from the Dutch Diabetes Research Foundation (DFN)
Postdoc: Emmani Nascimento