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Bacterial fragments from leaky gut help drive obesity, study shows

Fat cells are damaged by bacterial fragments that are released into the blood stream by a leaky gut, contributing to obesity and diabetes risk, new research suggests.

Fat cells
Fat Cells from adipose tissue (stock image)

Scientists at Nottingham Trent University found that microbe fragments called endotoxin enter the blood stream and directly impact how well fat cells function and their capacity to be metabolically active.

The normal gut contains millions of microorganisms that have essential roles in many aspects of human health.

In obesity, however, the wall of the gut can become impaired and leaky, allowing the release of these bacterial fragments into the blood, where they go on to travel through the body to different tissues.

The researchers say the study is a breakthrough in understanding the health of fat cells and how they drive weight gain and associated disease.

Dysfunctional body fat is known to contribute to metabolic disease, including Type 2 diabetes.

As part of the study the team was aiming to understand how significant weight loss may help to reverse the amount of endotoxin circulating in the blood to reduce the resulting damage to fat cells.

Using a series of experiments they found that fat cells are significantly damaged by endotoxin – and that this reduced their ability to transform into the more metabolically-active brown-like fat cells, which drive weight loss.

The study also found that white fat cells derived from participants with obesity were less likely to transform into brown-like fat cells compared with fat cells from lean individuals, likely due to the higher levels of endotoxin found in the blood of participants with obesity.

The team also examined how weight loss could reverse the circulating gut-derived endotoxin and resulting fat cell damage.
They found that weight loss surgical intervention, such as bariatric surgery, reduced the amount of endotoxin in the blood, which was also associated with improved metabolic health of the fat cells across the participants studied.

“Gut microbe fragments that enter the blood stream reduce normal fat cell function and their metabolic activity, which is exacerbated with weight gain, contributing to increased diabetes risk,” said lead researcher Professor Mark Christian, a scientist in Nottingham Trent University’s School of Science and Technology.

He said: “It appears that as we gain weight, our fat stores are less able to limit the damage that gut microbe fragments may cause to fat cells. Endotoxin from the gut reduces fat cell metabolic activity and its ability to become “brown-like fat cells” that can be useful to help lose weight. Our study highlights the importance of the gut and fat as critical interlinked organs that influence our metabolic health.

“This work has built upon previous studies by the team that show the importance of how gut-derived endotoxin damages our fat with weight gain. As such this work suggests the need to limit endotoxin-induced fat cell damage is even more important when you have excess weight, as the endotoxin contributes to reduce healthy cellular metabolism.”

Dr Alice Murphy, a postdoctoral research fellow at Nottingham Trent University added: “These studies with patients highlight that despite gaining weight, if we lose that weight, we can reverse the damage our gut can pose to our fat cells, which ultimately will have a major impact on our health and the benefits of weight loss.”

Researcher Dr Farah Omran added: “Brown-like fat cells are linked with overall healthy metabolism as they are highly metabolically active. We found that increased endotoxin levels, implicated in obesity, act to prevent their appearance and instead force the more unhealthy white fat cells to predominate.”

The study, which also involved the University of Warwick, is published in the journal BMC Medicine.

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    About Nottingham Trent University

    Nottingham Trent University (NTU) received the Queen’s Anniversary Prize for Higher and Further Education in 2021 for cultural heritage science research. It is the second time that NTU has been bestowed the honour of receiving a Queen’s Anniversary Prize for its research, the first being in 2015 for leading-edge research on the safety and security of global citizens.

    The Research Excellence Framework (2021) classed 83% of NTU’s research activity as either world-leading or internationally excellent. 86% of NTU’s research impact was assessed to be either world-leading or internationally excellent.

    NTU was awarded The Times and The Sunday Times Modern University of the Year 2023 and ranked University of the Year in the Whatuni Student Choice Awards 2023. It was awarded Outstanding Support for Students 2020 (Times Higher Education Awards), University of the Year 2019 (Guardian University Awards, UK Social Mobility Awards), Modern University of the Year 2018 (Times and Sunday Times Good University Guide) and University of the Year 2017 (Times Higher Education Awards).

    NTU is the 5th largest UK institution by student numbers, with approximately 40,000 students and more than 4,400 staff located across five campuses. It has an international student population of 7,000 and an NTU community representing over 160 countries.

    Since 2000, NTU has invested £570 million in tools, technology, buildings and facilities.

    NTU is in the UK’s top 10 for number of applications and ranked first for accepted offers (2021 UCAS UG acceptance data). It is also among the UK’s top five recruiters of students from disadvantaged backgrounds and was the first UK university to sign the Social Mobility Pledge.

    NTU is ranked 2nd most sustainable university in the world in the 2022 UI Green Metric University World Rankings (out of more than 900 participating universities).

Published on 22 May 2023
  • Subject area: Sciences including sport sciences
  • Category: Press office; Research; School of Science and Technology