Macrophage-mediated Inflammation in white adipose tissue and NAFLD.
Research type
Research Study
Full title
Understanding the role of macrophage-mediated inflammation in white adipose tissue and liver fibrosis.
IRAS ID
265876
Contact name
Jacques Behmoaras
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Research Summary
Non-alcoholic fatty liver disease (NAFLD) is present in one third of the population and due to its potential to cause irreversible liver damage and liver cancer, it is a significant health burden. There is a strong link between obesity and NALFD. As fat accumulates, the body is unable to process it, leading to unhealthy fat metabolism. Currently, other than lifestyle measures and better control of Type 2 Diabetes Mellitus (T2DM) with medication, there is no drug that can prevent or reverse the liver damage. Furthermore, there is no easy way to identify which person will go on to develop the liver damage.
Mounting evidence suggests that inflammation in the fat has a key role in driving liver damage, particularly by the immune cell called the macrophage. However, detailed mechanisms are lacking. Therefore, the aim of this proposal is to study obese patients with NAFLD to better understand the link between unhealthy fat metabolism and liver damage, focusing on identifying macrophage-derived drug targets which can potentially reverse the liver disease. Samples of fat and liver from patients who are having bariatric surgery at Imperial College Healthcare NHS Trust will be analysed to identify and target the inflammatory markers of unhealthy fat and NAFLD using genetic profiling techniques.
Summary of Results
Metabolic dysfunction-associated steatotic liver disease (MASLD) is present in one third of the population and some people can then go on to develop irreversible liver damage and liver cancer, making it a significant health burden. There is a strong link between obesity, MASLD and type 2 Diabetes Mellitus (T2DM). As fat accumulates, the body is unable to process it, leading to unhealthy fat metabolism. This can result in Type 2 diabetes(T2DM),and can in some people, lead to irreversible liver damage. Currently, other than lifestyle measures and better control of T2DM with medication, there is no drug that can prevent or reverse the liver damage. Furthermore, there is no easy way to identify which person will go on to develop the liver damage.
Therefore, the aim of this research was to better understand the link between unhealthy fat metabolism, T2DM and liver damage.Samples of fat, liver and blood from patients who were having bariatric surgery and lean patients undergoing surgery for other causes at Imperial College Healthcare NHS Trust were used to characterise the changes seen in the liver and fat as a result of obesity. We found that in obesity the structure of the fat tissue changes; the fat cells are bigger and there are alterations in collagens surrounding the fat cells which are important for maintaining their structure. The fat also becomes more inflamed with more inflammatory cells present in the tissue collected from the patients with T2DM.
As we knew that inflammation was an important change observed in the fat tissue in obesity, we also looked at a group of lipids(fats) that are associated with inflammation called the oxylipins. We measured their abundance in the liver, fat and blood and discovered that a group of oxylipins decreased in patients with obesity and MASLD or T2DM compared to patients without T2DM or MASLD.
This has helped us understand how obesity is affecting people’s organs and has added to what is known about how the liver and fat interact with each other when people start to develop liver disease and T2DM.
We are planning to continue investigating why these oxylipins change. We will also investigate further how the liver and fat interact with each other in obesity by looking at how individual genes and their signalling changes within the fat and liver cells to help us further understanding how these organs interact.
You can read the in-depth study which has been publish in a peer-reviewed journal eBioMedicine here.
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REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
19/WM/0229
Date of REC Opinion
8 Aug 2019
REC opinion
Further Information Favourable Opinion