08:47pm Saturday 11 July 2020

Scientists trace ‘bad’ fat back to its roots

The research, led by scientists in the Medical Research Council (MRC) Human Genetics Unit at the University of Edinburgh, is published today in the journal Nature Cell Biology.

There are two main types of fat in the body: subcutaneous fat, which sits directly beneath the skin and provides energy, cushioning and insulation; and visceral fat, which forms in six depots around the heart, intestines and other vital organs.

Studies have shown that having a lot of visceral fat increases the risk of cancer, type 2 diabetes, cardiovascular disease and Alzheimer’s disease, while subcutaneous fat is thought to be protective. Understanding where these two types of fat originate has posed a challenge to researchers, until now.

Using genetically modified mice, researchers show that the majority (up to 80 per cent) of visceral fat in the body can be traced back to a single type of cell in the developing embryo. These fat precursor cells, which express a gene called Wt1, are not found in subcutaneous fat, suggesting that ‘good’ and ‘bad’ fat come from different sources.

Cells expressing Wt1 were also found in the visceral fat of adult mice, where they continue to make more fat cells throughout their lifetime, in a similar way to stem cells. The highest number of these cells were found in the fat depots around the heart and stomach, which are known to be the riskiest places to carry excess fat.

Lead author of the study Dr You-Ying Chau, from the MRC Human Genetics Unit at the University of Edinburgh, said:

“Determining the origins of good and bad fat has been one of the big unanswered questions in obesity research. We’ve now shown that most bad fat comes from cells expressing the Wt1 gene in the later stages of pregnancy. 

“We also found that cells expressing Wt1 continue to act as a source of visceral fat into adulthood where they may be influenced by external factors such as diet. If we could find a way to control the regulation of these cells, we might be able to stop the body laying down any more bad fat around the organs. However, it will take many more years of research before we get there.”

The team also discovered that visceral fat, like the organs it surrounds, has its own protective membrane called a mesothelium. This too contains Wt1-expressing cells and can act as a source of visceral fat.

Professor Nick Hastie, leader of the research team and Director of the MRC Human Genetics Unit, part of the MRC Institute of Genetics and Molecular Medicine, at the University of Edinburgh, added:

“We found strong evidence for the existence of a mesothelium, which was a big surprise because nobody thought this membrane existed in fat. It seems that not only does the mesothelium help produce the cells that make the fat, it also surrounds the fat, making it into a neat little organ. In a way this makes sense because, otherwise, how would your body know to form fat and to package it around your heart or kidneys?”

The scientists also found that the different fat depots appear to have different properties, depending on how many Wt1 cells are present. They now hope to investigate how these cells behave in humans.

Professor Stephen Hill, Chair of the MRC’s Molecular and Cellular Medicine Board which funded the work, said:

“Visceral fat can be a silent killer because it’s possible to have a lot of it without looking fat on the outside. Studies like this one are important because they help us to understand how our genes and other biological factors are involved in regulating visceral fat, so that in future we can devise new ways to prevent or treat the devastating consequences of obesity.”

Image credit: Chau, et al and Nature Cell Biology.

Further information

Journalists with media enquiries should contact the MRC press office on 0207 395 2345 (out of hours: 07818 428 297) or email [email protected].

 

The paper, entitled ‘Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source’ by Chau et al, is published in Nature Cell Biology. URL when published: http://dx.doi.org/10.1038/ncb2922.


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