Determining the Fitness of Fat: Using FFC-MRI Imaging as a Novel Non-Invasive Method to Detect Changes in Adipose Tissue Health

Obesity is a major and increasing worldwide health problem and is linked to diseases including diabetes, cardiovascular disease and dementia. Finding new ways to tackle obesity and prevent the conditions associated with it is a key healthcare challenge.

One exciting avenue is to harness the ability of a specialised type of adipose tissue to burn lipids as a fuel source and then waste the energy as heat. A key limitation in studying this is the difficulty in discriminating between lipid-storing and lipid-burning adipose tissue using current imaging methods.

This project will employ a novel imaging method called fast field-cycling magnetic resonance imaging (FFC-MRI) which we have recently shown can discriminate between these different types of adipose tissue. The project will refine the methods for doing this and apply it to in vivo studies of genetic and nutritional modifications that may alter lipid oxidation and adipose tissue function to prevent obesity and associated metabolic diseases.

Project Detail:

Although excessive adipose tissue accumulation defines obesity, adipose tissue is not inherently bad for health. Rather, when fat cells (adipocytes) become overloaded they can no longer to act as a safe store for nutrients, particularly lipids (1,2). These lipids then spill over to other tissues causing disease. This has led to a great deal of interest in understanding how adipose tissue can be maintained in a healthy state in order to prevent obesity related disease.

Adipose tissues in different parts of the body have different properties. Most body fat is white adipose tissue (WAT), which is specialised in storing lipids. WAT depots have varying metabolic roles. The expansion of subcutaneous WAT is generally protective against metabolic disease whilst increased visceral WAT is typically associated with ill-health (2). Brown adipose tissue (BAT) is able to oxidise lipids and then dissipate the resulting energy due to uncoupled respiration. This generates heat so that BAT effectively ‘burns’ rather than storing lipids (1). Some WAT adipocytes also have an inducible, lipid-oxidising, BAT-like capacity and are known as ‘brite’ (for brown in white) adipocytes.

There is significant interest in increasing the amount of brown or brite adipocytes as a treatment for obesity, using either pharmacological or nutritional interventions. However, a major limitation in such studies is the difficulty of reliably quantifying different types of fat, particularly brown/brite fat in humans (3). We have recently discovered that FFC-MRI may offer a novel, non-invasive way to image BAT. FFC-MRI has some major advantages over other methods for the detection of BAT as it does not require expensive chemical tracers and does not involve exposure to ionising radiation. Uniquely, FFC-MRI may also be able to distinguish between healthy and unhealthy WAT tissue. This exciting new finding implies that FFC-MRI may allow us to observe changes in WAT as it becomes metabolically unhealthy, as occurs in obesity and associated metabolic diseases. This would allow us to identify individuals at risk of developing metabolic diseases before this occurs.

Specifically this project will:

1.Further refine the use of FFC-MRI to image different types of adipose tissue and map the precise metabolic characteristics of the adipose tissue to the FFC-MRI signature we observe.
2.Use FFC-MRI with a range of other analyses to define metabolic changes in different adipose tissue depots in in vivo models of altered lipid oxidation and energy expenditure. This will include dietary interventions, environmental challenges and genetic modifications such as the disruption of gamma-synuclein, which protects from the development of obesity by increasing lipid oxidation.
3.Apply FFC-MRI in humans as a novel tool for imaging BAT and to discriminate between metabolically different WAT adipose tissues.

Overall, this project will develop the use of FFC-MRI as an exciting new non-invasive imaging tool for the study of adipose tissue function and apply it to ask key questions regarding the potential for altering adipose function to prevent or treat metabolic diseases.