The past decade has witnessed a surge of interest into how we can harness adipose tissue to help fight obesity and other metabolic disorders. One promising approach involves utilising adipose tissue to burn off excess energy stores, in the form of heat. This process occurs naturally in the brown adipose tissue of mammals, most notably in hibernating or cold-temperature species that require extra generation of heat to keep warm, and also in infant humans. Recently it has been shown that white adipose tissue, which we most commonly associate with storage of body fat, can itself assume a ‘brown’ phenotype. This enables it to burn off stored up lipids as heat by uncoupling the mitochondrial electron transport chain from ATP production.

The ‘browning’ of white adipose tissue is tightly controlled and we are only beginning to understand how this process is regulated. Efforts have largely been directed towards elucidating the transcriptional control of browning in response to environmental cues. Our group studies the transcriptional repressor Krüppel-like factor 3 (KLF3), which has been implicated in adipose biology since it was first discovered that mice lacking KLF3 were lean with reduced fat mass, and remained this way when fed a high-fat diet.

In addition to reduced adiposity, the white adipose depots of KLF3 knockout mice exhibit a ‘browner’ appearance, indicative of increased mitochondrial content – a key aspect of browning. The expression of important mitochondrial and thermogenic genes is elevated in knockout adipose tissue, including Ucp1, Elovl3 and Cidea. We have also shown by flow cytometry that eosinophils are more prevalent in the fat of KLF3 knockout mice, another hallmark of the brown-in-white phenotype.

Future work will centre on determining the underlying mechanisms that lead to enhanced browning of white adipose tissue. Bone marrow transplantation experiments will provide an insight into the contribution of tissue-resident blood cells, while cold temperature studies and treatment with beta-adrenergic receptor agonists will allow us to better understand the relationship between environmental cues and transcriptional control of the process.