Shifting perspectives on fatty tissue

Fatty tissue, or adipose tissue, is found throughout the body and is made up of fat cells called adipocytes. Its main role is to serve as an energy reservoir, but it also insulates our bodies, cushions our organs and secretes hormones.  

As our understanding of fat cell biology advances, so too is the way that we think about fat and its role in health and diseases such as type 2 diabetes. While society often considers fat as a bad thing, the latest research shows that the healthy growth and expansion of fatty tissue has protective qualities for our bodies. It’s only when fatty tissue loses its ability to expand and contract and fat begins to accumulate around our organs that it becomes toxic. The health of fatty tissue is maintained by the continuous generation of new fat cells from early fat cells, known as stem cells, to replenish the tissue. In obesity, this process has to happen a lot more because of the various stresses obesity places on the body. This can cause stem cells to become ‘exhausted’ and lose their health. Preserving the health of these stem cells could therefore hold the key to preventing obesity and associated diseases.  

Introducing Alice

Alice has dedicated her career to studying fatty tissue. Her initial interest developed while working on her PhD in the Cellular Stress Group, led by Professor David Carling at the LMS. During this time, she studied mice with a mutation causing high levels of an enzyme called AMP-activated protein kinase (AMPK) to be made. AMPK is an energy sensor in our cells, coordinating metabolic pathways to balance energy supply, or nutrients, with energy demand. Different cells burn substances for energy in different ways. These mice developed fatty tissue which burned fat in a more metabolically active way, similar to how muscles burn fat, using a system known as calcium futile cycling. The finding that AMPK activation led to the development of stem cells capable of producing fat cells that burn fat via this calcium futile cycling mechanism led to Alice’s interest in how metabolism regulates stem cell fate. 

Following a postdoctoral position with the pharmaceutical company AstraZeneca, Alice was awarded a prestigious Biotechnology and Biological Sciences Research Council (BBSRC) Discovery Fellowship to independently lead her own work at the LMS and the Insitute of Clinical Sciences, Imperial College London. Now in the final year of her fellowship, she is focusing on understanding the role of AMPK in the formation and accumulation of fatty tissue, a process known as adipogenesis. While working at the LMS, her close ties with clinicians at Imperial College Healthcare NHS Trust have enabled her to extend her work from mice to human tissue, by collecting samples from consenting patients undergoing weight loss surgery. This is facilitated by Imperial College Healthcare Tissue Bank. Getting a license and the appropriate ethics approval to do this is a timely process making this a rare achievement for scientists. Alice’s goal is to understand how we can preserve stem cell health in fatty tissue to prevent people with obesity developing metabolic diseases like diabetes, which are driven by stem cell exhaustion, ultimately improving and extending their lives. 

Unique insights into the formation of fatty tissue

Up until recently, scientists knew little about the role of AMPK in fat stem cells. In February 2024, Alice published exciting work in Biochemical Journal showing that activating AMPK suppresses leptin – a hormone released by fat cells that helps your body maintain normal weight by regulating appetite. This was the first time scientists demonstrated an effect of AMPK on leptin alone. 

Sophia Bustraan, a PhD student under Alice’s supervision, treated fat stem cells from normal, also known as wild-type, mice with a molecule to activate AMPK, called BI-9774, during critical stages of fatty tissue formation. She found that AMPK activation suppresses fatty tissue formation in a time- and concentration-dependent manner and notably inhibits leptin regardless of fatty tissue formation. Obesity causes the body to produce high levels of leptin, leading to leptin resistance, which means people can no longer control their appetite. This is similar to how people develop insulin resistance in response to unhealthy diets in type 2 diabetes. High leptin can also cause inflammation and insulin resistance, which contribute to the development of type 2 diabetes.  AMPK’s role in inhibiting leptin therefore indicates a pathway that researchers could exploit for therapies to treat obesity or associated metabolic disorders. This study was the first of its kind to use AMPK activators at concentrations similar to those found naturally in our bodies, addressing potential off-target effects seen in much of the research in the field which uses AMPK activators at very high levels. Alice discusses these findings and the potential of AMPK activators in promoting healthy fat cell development in a review published in Essays in Biochemistry in August 2024, arguing for the importance of promoting healthy fatty tissue expansion rather than just inhibiting fatty tissue formation. 

Recognising scientific excellence

Alice’s contributions to the field were recognised this year when she was selected to attend the 21st Global Annual Meeting of the Science and Technology in Society (STS) forum in Kyoto, Japan during October 2024 as part of its Young Leaders Program. 

The program invited around 140 research leaders from across the world to attend alongside nine Nobel Laureates and leaders from a variety of sectors including the pharmaceutical and tech industries. The event hosted a wide range of talks, many of which had a strong focus on the integration of artificial intelligence (AI) into biotech and medicine, and the importance of standardising data for this purpose. 

The LMS: Discovery science for human health 

Alice is now in the final year of her fellowship and is seeking new leadership opportunities to continue her work at the LMS in fatty tissue formation and its role in obesity and metabolic disease. Importantly, metabolic diseases such as type 2 diabetes are a major factor in multimorbidity. Multimorbidity – or living with two or more long-term conditions – has become a central challenge to human health as the life expectancy of populations has increased, creating complex problems for managing patients.  

Our discovery science excellence spanning research into cell identity, sex differences and gene-environment interactions make the LMS highly suited to lead on the integrated investigation of mechanisms underlying metabolic diseases and multimorbidity. 

We are excited to see the progress that Alice makes in this field in the years to come and that her achievements as a Future leader in scientific research are being recognised on the international stage. Congratulations Alice!