Genetic mechanisms regulating white adipose tissue plasticity
Adipose tissue plays a central role in energy and glucose homeostasis and can be mainly partitioned into subcutaneous and visceral fat. These two types are also functionally different which becomes evident during visceral fat expansion, which is strongly associated with a high risk of developing obesity associated metabolic complications including type 2 diabetes.
This discrepancy is largely due to regional differences in adipocyte behaviour including adipokine secretion and rates of lipolysis and triglyceride synthesis. Understanding the genetic mechanisms that are responsible for such intrinsic differences between distinct adipose tissue depots may help to find novel strategies to improve metabolic health. We recently identified that glucocorticoids induce a gene called LMO3 specifically in human but not mouse visceral preadipocytes necessary for efficient adipocyte differentiation (Lindroos et al., 2013). As LMO3 is expressed highly in mature adipocytes, we aim to determine the role of LMO3-dependent pathways in the modulation of key functions of visceral adipocytes during obesity.
Brown and beige adipose tissue development
Increasing brown adipose tissue thermogenesis may help to control body weight and prevent metabolic disorders. Recently, screening brown adipose tissue using RNA-Seq led us to identify the long noncoding RNA H19 as an important regulator of brown fat cell formation and function. High activity of H19 in mice prevented diet-induced weight gain (Schmidt et al., 2018). We will continue to compare human and mouse adipose tissues using a combination of long and short-read Next Generation Sequencing methods to identify and functionally validate potential novel regulators of brown and beige fat.
In another project, we will apply our tissue-specific transgenic models to elucidate Heme Oxygenase-1 dependent pathways controlling brown and beige fat formation and function.
Techniques and infrastructure of the research group
Major techniques include various RNA-Seq protocols based on long and short-read Next Generation Sequencing methods, cell respiration analysis, adipogenesis assays as well as glucose and lipid metabolism assays. The group utilizes tissue-specific mouse models to study white and brown adipose tissue development and function. Group members have access to a fully equipped cell culture facility, PCR equipment (incl. multichannel Real-time PCR) and a fluorescent microscope with imaging equipment.