RESEARCH
BACKGROUND
Adipocytes under the fluorescent microscope. In red you can see the cell membranes and in blue you can see the nuclei of the cells. Note the large lipid laden droplet in the middle of each adipocyte (unstained and thus completely black).
In the past decades the prevalence of obesity has risen explosively and is predicted to continue rising. Obesity, defined as having an excess of adipose tissue, is associated with the metabolic syndrome and comprises of a cluster of metabolic disorders, including insulin resistance, dyslipidemia and hypertension. These disorders are risk factors for developing diabetes and cardiovascular disease. Obesity also increases the risk for many types of cancers, associates with poor cancer outcome, reproductive problems, osteoarthritis, kidney disease and fatty liver disease.
An important factor behind obesity complications is the fat cell (adipocyte). Adipocytes release large amounts of free fatty acids which regulate insulin action and the metabolism of glucose and lipids in skeletal muscle and liver. They also secrete hormones, inflammatory proteins and other substances with peripheral effects on blood vessels, appetite, energy homeostasis, blood pressure and glucose as well as lipid metabolism. Thus, disturbances in the normal functioning of fat cells have significant consequences on the health of an individual. Despite the importance of the fat mass very little is known about the maintenance of fat cells in humans, how different fat depots are regulated and how, or if, this is altered in obesity. In the Spalding Lab we hope to contribute to a better understanding of adipocyte biology and lipid metabolism.
PROJECTS
ADIPOCYTE AND LIPID TURNOVER
Lipid turnover and cell age are studied using radiocarbon dating. By studying cell turnover in a variety of different adipose depots (such as various subcutaneous adipose depots as well as visceral depots) we aim to better understand the regulation of the fat mass in humans. Understanding the dynamics of adipocyte and lipid turnover may shed new light on potential treatments for obesity.
C14 levels in lipid samples compared to atmospheric C14 levels (Arner et al. Nat Med. 2019)
The C14 levels this research uses, are caused by above-ground atomic bomb detonations
BAT MAPPING
A long-held dogma in adipose biology has been that adult humans do not possess brown adipose tissue (BAT). However in the late 2000s, this dogma shifted as PET-scans revealed that adult humans do have active BAT. Up until now, however, a systematic investigation on the histology of the different BAT depots in the human body has not been executed. In this project we map the BAT depots and investigate the influence several physical parameters have on these tissues.
Expression of the canonical BAT marker (UCP1) in BAT adipose tissue (Unpublished data, Spalding Lab).
SENESCENCE
Cellular senescence is a process in which cell cycle progression is irreversibly halted and this can lead to cells having trouble fulfilling their function and negatively affecting neigbouring cells. Senescence is studied using a variety of molecular techniques such as immunocytochemistry and assays for markers of senescence with the aim of better understanding the links between obesity and other diseases.
SABG-staining is one of the main lines of evidence of cellular senescence and the fraction of SABG positive adipocytes is much higher under hyperinsulinaemic conditions. (Li et al., Nature medicine. 2021)
WAT BROWNING
There are two main types of adipose tissue, white adipose tissue (WAT) and brown adipose tissue (BAT). WAT adipocytes store energy in the form of lipids as well as having important endocrine functions. BAT adipocytes burn nutrients, produce heat and increase total energy expenditure. A third type of adipose tissue, brite or beige fat, arises from WAT browning. Brite/beige cells are found in WAT depots and can be ‘browned’ by different stimuli. In this project we study the capacity of WAT to undergo browning treatments in the context of obesity and diabetes.
BAT marker expression upon a browning treatment. (Harms et al. Cell Reports. 2019)