Although fat cells (adipocytes) normally function as part of the immune system and help control lipid accumulation, the extracellular environment in obesity traps a vicious cycle of inflammation, increasing risk of several major disease. 24 hours is all it takes for a so-called precursor fat cell to have its 'epigenetic recipe' on how to correctly develop into a mature fat cell, reprogrammed.
This change occurs when the cell is put into contact with the fatty acid palmitate or the hormone TNF-alpha, a study conducted by researchers from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen shows.
Precursor cells are cells that have not yet matured to undertake a specific function in the body, e.g. the function of a muscle or fat cell. Palmitate and TNF-alpha are able to disturb the development of the cell, causing it to develop into a dysfunctional fat cell later in its life. In particular, this reprogramming is found in obese patients suffering from type 2 diabetes, the researchers have found.
While fat in the hip/thigh region is mainly stored just under the skin, fat in the midsection is also stored deeper inside the body, in and around the liver and other organs. Fat cells deep in the abdominal area apparently behave differently than fat cells under the skin of the thighs and hips. In scientific lingo, these fat cells are more metabolically active. They may release different substances, for example, more fatty acids which could explain some of the adverse effects.
We are exposed to palmitate through the food we eat. Especially foods containing large amounts of saturated fat such as dairy products, meat and palm oil are plentiful in palmitate. TNF-alpha is an inflammatory hormone that is secreted in the body during illness. Obese patients also have a higher level of TNF-alpha, as obesity is linked to inflammation.
'Our results stress the importance of a healthy diet and lifestyle for our metabolic health in the years to come. To a large extent, a healthy diet and healthy lifestyle can help prevent the reprogramming of our precursor cells. In the long term, we hope our study may be at the origin of new strategies to reverse the abnormal programming of fat precursor cells, making them healthy and functional once again', says Romain Barres, who is at the head of the study.
Environmental Factors Play a Key Role
Within so-called epigenetic research, several studies have suggested that human precursor cells have a memory of past environmental exposures. But until now no one has been able to identify the factors affecting the reprogramming of precursor fat cells or establish the rapidity at which cells are reprogrammed.
In cooperation with the Surgical Gastroenterology unit at Hvidovre Hospital, the researchers collected fat tissue from 43 planned operations. 15 patients were lean, 14 were obese and 14 were obese and suffered from type 2 diabetes. By collecting samples from three different groups of patients, the researchers were able to compare the health of the precursor fat cells of the three groups.
The team learned that the cells from the group of obese patients suffering from type 2 diabetes had been reprogrammed and therefore did not function like normal, healthy fat cells. By exposing healthy precursor fat cells to the two external factors for just 24 hours the researchers were able to mimic the reprogramming they had observed in cells from the diabetic patients.
A Promising Research Area
The researchers are unsure whether it is possible to reverse the programming to make the cells healthy and functional again. And even if it is possible, they do not know how to do it.
'We now know that precursors cells can be reprogrammed in a way that function is impaired at the final stage of their development, but so far no one has discovered how to reverse the process. But it is a promising field', says Romain Barres.
Imagine that the cells in our organs have a recipe book with programmes telling them how to develop into mature cells. The programmes tell the cells within our fat tissue which pages of the book to read in order to develop into fat cells. However, exposure to large amounts of palmitate or TNF-alpha causes the cookbook to change. Now the cells do not have access to all the pages of the book, and they will not be able to develop in the right way. They still develop into fat cells, but they are dysfunctional.