April 2016 | Aibreán 2016

Lowering Cardiovascular Disease Risk in Obesity

Thu, 21 April 16 15:04

New research findings indicate that replacing dietary carbohydrate with monounsaturated fat in otherwise obesogenic diets is better for the cardiovascular health. The international collaborative study led by Dr Fiona McGillicuddy, Conway Institute Fellow, also identified specific inflammatory proteins that could be used as novel biomarkers to flag patients who have difficulties with eliminating cholesterol from the body.

Chronic inflammation is a hallmark of both obesity and cardiovascular disease. Scientists believe that the process of removing cholesterol from the body is important in reducing the risk of developing cardiovascular disease. Dr McGillicuddy previously demonstrated that induction of inflammation reduces cholesterol elimination from the body and prompted her to investigate whether chronic inflammation observed in obesity might have similar effects.

High density lipoprotein (HDL) particles circulating in the blood collect cholesterol from peripheral cells and transport it to the liver, and then to the bowel for elimination in faeces. These HDL particles also carry a large cargo of proteins, some of which cause inflammation and others that prevent inflammation.

Previous studies have shown that merely increasing the quantity of these cholesterol transporters (HDL-C) has no clinical benefit. This study set out to investigate how obesity affects the protein cargo on HDL particles and to determine if there was a difference in these proteins when obesity was brought about by a monounsaturated fat-enriched diet or a saturated fat-enriched diet.

The research team showed that both high-fat diets raised HDL-C levels. However, the process of eliminating cholesterol from the body was most effective after monounsaturated fat diet and, importantly, did not result in liver inflammation. Instead, proteins that reduce inflammation were enriched on the HDL particles after a monounsaturated fat diet.

By contrast the saturated fat diet caused inflammatory proteins from the liver to join to HDL particles, which coincided with reduced transport of cholesterol through these inflamed livers.

Dr Fiona McGillicuddy, a member of the Diabetes Complications Research Centre explained,

“While dietary replacement of carbohydrate for fat may normalise lipid profiles in obesity, our study warrants caution over the fat quality.”

“By looking in detail at the complex protein signature of HDL-C, we are able to reveal the presence of inflammatory proteins derived from the liver after prolonged saturated fat intake that reflect impaired cholesterol elimination. On the other hand, a monounsaturated fat diet increased the efficiency of eliminating cholesterol from the body with none of the unwanted side effects of inflammation.”

The research was carried out in conjunction with colleagues in the Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine in the United States. The team will now focus on determining whether anti-inflammatory interventions can reduce liver inflammation and rescue cholesterol trafficking to faeces in obesity.

Dr McGillicuddy received funding through the Science Foundation Ireland-Health Research Board - Wellcome Trust Biomedical Partnership to determine whether the type of diet that causes the obesity also plays a role in elevating the risk of coronary artery disease.

Lowering cardiovascular disease risk in obesity

Extracted image from figure 3 O'Reilly et al Circulation Apr 14, 2016 doi: 10.1161/CIRCULATIONAHA.115.020278.

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Original article published by UCD Conway Institute. Reproduced with permission.