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.

The C14 levels this research uses, are caused by above-ground atomic bomb detonations

C14 levels in lipid samples compared to atmospheric C14 levels (Arner et al. Nat Med. 2019)

Mapping brown fat

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.

Expression of the canonical BAT marker (UCP1) in BAT adipose tissue (Unpublished data, Spalding Lab).

Adipocyte senescence

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.

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)

Fat cells and breast cancer

Obesity is a well-known risk factor for breast cancer and is associated with worse outcomes for patients. Fat cells, also called adipocytes, make up much of breast tissue and play an active role in influencing the environment of breast tumors and how cancers grow and spread.

Obesity can alter the behavior of fat cells in significant ways. One such change is a process called cellular senescence. During this process, cells essentially enter a "retirement phase": they stop dividing but do not shut down completely. Instead, they remain active and release signals that can reshape their surroundings and influence nearby cells.

This project explores how obesity-related changes in adipocytes impact triple-negative breast cancer (TNBC), one of the most aggressive and difficult-to-treat types of breast cancer. By studying how senescent fat cells interact with tumor cells and their environment, we seek to gain new insights into breast cancer biology and identify potential treatment strategies.

White adipocyte browning

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)