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Scientists unlock how trans fats harm arteries

By Nathan Gray , 03-Nov-2010
Last updated on 03-Nov-2010 at 17:41 GMT

The method by which dietary trans fats cause hardening of the arteries (atherosclerosis) may have been identified by a new study on mice fed a high trans fat diet.

The research paper, published in The Journal of Nutritional Biochemistry, suggests that high levels of trans fats cause atherosclerosis by reducing the responsiveness of a key protein that controls growth and differentiation in cells. The protein, known as transforming growth factor (TGF)-beta, plays an important role in immunity and the development of heart disease, diabetes and cancer.

The findings of the study reinforce recent moves by industry to move away from the use of trans fats after studies linked the predominantly man-made fat with a range of health problems.

“Our demonstration that suppression of TGF-beta responsiveness (in aortic endothelium and possibly in other tissues) caused by dietary trans fats is likely to have important implications in other trans fat-related diseases and disorders,” stated the researchers, led by Dr. Chun-Lin Chen from Saint Louis University School of Medicine, in the U.S.

“For example, it has been postulated that trans fats are carcinogenic and also contribute to autoimmune disease. These phenomena might be due to suppression of cellular TGF-beta responsiveness by dietary trans fats – since TGF-beta is a well-known tumour suppressor and immuno-suppressor,” they added.

Trans fat risk

Though trace amounts of trans fats are found naturally, in dairy and meats, the vast majority are formed during the partial hydrogenation of vegetable oil (PHVO) that converts the oil into semi-solids for a variety of food applications.

Trans fats are attractive for the food industry due to their extended shelf life and flavour stability, and have displaced natural solid fats and liquid oils in many areas of food processing.

But scientific reports that trans fatty acids raise serum levels of LDL-cholesterol, reduce levels of HDL-cholesterol, can promote inflammation can cause endothelial dysfunction, and influence other risk factors for cardiovascular diseases (CVD), has led to a well-publicized bans in New York City restaurants, and other cities, like Chicago.

In the food industry this has been mirrored by an increase the in pressure on food manufacturers to reduce or remove trans fatty acids from their products and reformulate.

The food industry as a whole has expressed its commitment to removing trans fatty acids from its products, but such reformulation is not straightforward and presents challenges.

Despite the well accepted link between trans fats and heart health, the St Louis-based scientists claim that the mechanisms by which trans fats cause atherosclerosis and other diseases remain unclear.

Chen and colleagues stated that there is “accumulating evidence” to indicate that transforming growth factor (TGF)-beta in the circulation protects against atherosclerosis. They stated that previous studies have found that suppressed TGF-beta responsiveness in the walls (endothelium) of the aortic blood vessel plays an important role in the development of atherosclerosis in animals.

The researchers fed mice a high-trans fat (Western) diet or a control diet of standard rodent chow and tested the effects dietary trans fat intake on TGF-beta after 16 or 24 weeks.

Mechanisms

The researchers observed that normal mice fed a high trans fat diet for 24 weeks exhibited atherosclerotic lesions and suppressed TGF-beta responsiveness in the aortic endothelium.

High trans fat mice also showed increased integration of cholesterol into tissue plasma membranes.

The authors reported a 24-week trans fat diet increased the expression of VCAM-1 – a marker of early lesions of atherosclerosis – four-fold compared to mice fed the control diet, corresponding to significant atherosclerotic lesions found in mice fed the trans fat diet.

However, the authors also reported that when mice were switched from the high trans fat diet to control diets at 16 weeks, markers of atherosclerosis, including TGF-beta responsiveness and VCAM-1 expression began to return to normal levels.

Suppressed responses

Dr. Chen and colleagues indicated that their results suggest that dietary trans fats cause atherosclerosis, at least in part, by suppressing TGF-beta responsiveness.

“This effect is presumably mediated by the increased deposition of cholesterol into cellular plasma membranes in vascular tissue, as in hypercholesterolemia,” they added.

Source: The Journal of Nutritional Biochemistry
Published online ahead of print, doi: 10.1016/j.niox.2010.10.002
“A mechanism by which dietary trans fats cause atherosclerosis”
Authors: C.L. Chen, L.H. Tetri, B.A. Neuschwander-Tetri, S.S. Huang, J.S. Huang

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