Looking at the role of matrix metalloproteinases in metabolic syndrome and non-alcoholic fatty liver disease.
Medical Student Prize Winner
“The role of matrix metalloproteinases in metabolic syndrome and non-alcoholic fatty liver disease”
Within the UK, as well as globally, non-alcoholic fatty liver disease (NAFLD) affects around 32% of the adult population.
Ms Shah based her project within the laboratory, looking at matrix metalloproteinases (MMPs) and how they react with each other in the development of NAFLD.
Ms Shah explains:
The mechanisms underlying the development of NAFLD from metabolic symptoms are complex. One of the structures implicated in NAFLD is the extracellular matrix (ECM), which has to be remodelled to allow inflammation to spread, and tissue to grow. The ECM is heavily regulated by MMPs, but if these are differently expressed, it can lead to ECM dysfunction and support disease progression.
In our research group, some genetically modified mice were bred without one of the MMPs known as Mmp28 (Mmp28KO mice). Surprisingly, even though these mice had a normal diet they developed the metabolic syndrome. In my project, I used histology and immunohistochemistry to determine whether Mmp28KO male mice showed any signs of NAFLD. I also looked at the gene expression of other Mmps and Timps, relevant to NAFLD, to see if Mmp28 deletion changed this.
I found that Mmp28KO mice had more fat and inflammation in their livers – an indication that they NAFLD – compared to wildtype mice. I also found that there were gene expression changes in Mmp28KO mice compared to wildtype mice, which were indicative of increased inflammation occurring.
Why did you choose this project?
“My project successfully managed to identify NAFLD in Mmp28KO mice and show that changes in Mmp mechanisms may be impacting the development of NAFLD and metabolic syndrome. With further research into these mechanisms, hopefully some day they may be used as therapeutic targets for drugs against metabolic syndrome and NAFLD.
This project complemented the career I want to pursue, which hopefully will include a combination of clinical and research responsibilities in internal medicine, with a focus on preventative medicine.”
This was my first experience of lab work and it really opened my eyes to the almost endless diversity of medical research. Additionally, it was incredibly rewarding to be part of a project on a subject that affects so many people now and will continue to do so in the future. I am grateful to GUTS UK and Dr Falk Pharma for recognising the potential of my work; this prize has encouraged me to keep seeking out new opportunities in research alongside clinical medicine.- Radhika Shah