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Malnutrition, shaping up to be a first world problem

July 17, 2016

SYDNEY, MONDAY 18 JULY, 2016: Australian researchers have discovered that a bad diet has consequences on your immune system even before you notice an increase in body weight.

Scientists from the Australian Research Council Centre of Excellence in Advanced Molecular Imaging have investigated the impact of a western-style high fat diet on our immune system, with two quite surprising results.

The link between diet and immunity and the ability of nutrition to speed-up or slow-down our immune response has long been suspected. This new research, published in the Journal of Immunology, shows that our immune system can be affected by diet prior to weight gain and other clinical signs of obesity.

Lead author, Dr Abigail Pollock, University of New South Wales (UNSW), says excess body fat can cause severe health problems.

"Obesity is now a huge financial burden to the health systems of many Western countries," she says.

"The World Health Organisation reported in 2014, that more than 1.9 billion adults were overweight, and of these over 600 million were obese.

"But what if immune dysfunction occurs before obesity?" Dr Pollock says. "Our research looked at whether bad diets have consequences before we notice an increase in body weight. And we found that the over consumption of saturated fats is a form of malnutrition: one that needs to be taken seriously."

To identify mechanisms in which a diet rich in saturated fats, can impact immune function the researchers examined the impact of dietary lipids on a class of immune cells - T lymphocytes, or T cells.

"We fed mice a Western-style high fat diet for nine weeks to observe if this diet would impact the T cell response before the animal gains weight," Dr Pollock says.

"Despite our hypothesis that the T cell response would be weakened we actually saw the opposite: the percentage of T cells multiplying increased."

One clinical ramification of overactive T cells may be autoimmune disease - diseases where the immune system begins attacking healthy parts of the body.

UNSW Professor Kat Gaus, Deputy Director of the Imaging CoE, says the other unexpected finding was that T cell responses were altered even in the absence of obesity and obesity induced inflammation.

"Our lab has previously shown altering the lipid content of T cell membranes, artificially, changes the T cell response. So, we devised this experiment to see if the same structural changes would occur naturally through a high fat diet," says Professor Gaus.

"The team set out to demonstrate that nutrition is able to directly impact immune function," she says.

And the results reveal that dietary lipids do in fact directly influence T cell activation and responsiveness by altering the composition and the structure of the T cell membrane.

"T cells are actually effected prior to the mice becoming overweight," says Dr Pollock. "Lipids in the diet change the abundance of lipids in the cell membrane, which in turn changes the structure of the cell altering the responsiveness of the T cells and changing the immune response," Dr Pollock says.

Where to from here?

"We now know that dietary lipids have the ability to directly affect T cell function through changing the lipid composition of the cell. Further research is needed to work out the link between lipids and T cell function so that we better understand which fats we should avoid," Professor Gaus says.

"To do this, we would remove the T cells from the mice and then conduct imaging or microscopy experiments on the cells to watch if and how the signaling changes compared with cells that have not undergone structural changes do to dietary intervention," Dr Pollock concludes.
-end-
For interview: Dr Abigail Pollock, Professor Kat Gaus

Contact: Stephanie Pradier stephanie.pradier@monash.edu 0424 568 314

Background information: T lymphocytes (T-cells) are an essential cellular component of the adaptive immune system that play a fundamental role in the elimination of invading pathogens.

Our T cells roam our body searching for diseased and/or infected cells, and although different types of T cells exist the common way in which they are triggered to defend our body is via the T cell receptor. This T cell receptor is located within the T cell membrane, the outer structural barrier of the cell, which makes the composition of the membrane important for the T cell response.

The membrane domain (i.e. the structure of the surface of the T cell and the arrangement of the lipids and cholesterol in the T cell) plays an important, but not yet well understood, role in the activation of the immune response. This study looked at how introducing fatty acids in the diet changed the internal lipid and cholesterol ratio of the T cell.

Cholesterol is found in every cell of your body. It is especially abundant in the membranes of these cells, where it helps maintain the integrity of these membranes, and plays a role in facilitating cell signaling -- the ability of your cells to communicate with each other so you function as a human, rather than a pile of cells.

What was surprising about this research was that when the mice consumed greater amounts of saturated dietary lipids, the percentage of cholesterol within the cell was reduced and the percentage of phospholipids increased, which induced a subtle change in the membrane composition. The results show that this change in the order of the membrane can have large effects on receptor signalling, T cell responses and triggering and downstream activation.

Full publication available online: http://www.jimmunol.org/content/196/10/3993.full

Stats on Australian obesity rates: http://www.abs.gov.au/ausstats/abs@.nsf/mf/4364.0.55.001

Further details: The $39 million ARC-funded Imaging CoE develops and uses innovative imaging technologies to visualise the molecular interactions that underpin the immune system. Featuring an internationally renowned team of lead scientists across five major Australian Universities and academic and commercial partners globally, the Centre uses a truly multi scale and programmatic approach to imaging to deliver maximum impact.

The Imaging CoE is headquartered at Monash University with four collaborating organisations - La Trobe University, the University of Melbourne, University of New South Wales and the University of Queen

Monash University

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