Study reveals how the brain can use fatty acids to control liver lipid production

Ways of keeping the heart healthy has widened, with the discovery that the brain can help fight off hardening of the arteries.

Atherosclerosis--hardening and narrowing of the arteries--can be caused by fat build up that causes plaque deposits, and is one of the main causes of cardiovascular disease. Jessica Yue, a newly recruited researcher in the Department of Physiology in the Faculty of Medicine & Dentistry, has shown a link between how the brain can regulate fat metabolism, potentially stopping the development of this disease risk factor in obesity and diabetes.

Her findings, published this month in Nature Communications, the online version of the high-impact Nature publication, outlines how the brain can use the presence of fatty acids, which are building blocks of fat molecules, to trigger the liver to reduce its own lipid production.

"We know that when there is dyslipidemia, or an abnormal amount of fat in the bloodstream, it's dangerous for health--largely because this can lead to obesity, obesity-related disorders such as Type 2 diabetes, and atherosclerosis," says Yue, and that "if you can find ways to lower fats in the bloodstream, it helps to lower these chances of diabetes and cardiovascular disease as a result of this atherosclerosis."

Yue trained at the Toronto General Research Institute under Tony Lam, where she was a recipient of fellowships from the Canadian Institutes of Health Research (CIHR) and the Canadian Diabetes Association. With her associates in Toronto and with Peter Light, professor of pharmacology in the Faculty of Medicine & Dentistry, she looked at how the infusion of oleic acid, a naturally occurring monounsaturated fatty acid, in the brain "triggers" a signal from the hypothalamus to the liver to lower its fat secretion, which Yue says is a "triglyceride-rich, very-low-density lipoprotein. Light is the co-author of Yue's paper in Nature Communications and is the director of the Alberta Diabetes Institute (ADI), where Yue is applying for membership.

"This fat complex is the kind of lipoprotein that is dangerous when its levels in the blood are elevated because it promotes atherosclerosis," she says.

The catch, though, is that this "trigger" doesn't work in obesity, a setting in which blood lipid levels are usually high. "In a model of diet-induced obesity, which then leads to insulin resistance and pre-diabetes, oleic acid no longer provides the fat-lowering trigger to the liver." Yue's findings, though, demonstrate how this faulty signal can be bypassed, unveiling potentially other ways to trigger this same function in obese patients.

This study could potentially impact how obesity and diabetes are treated, says Yue, which is the focus of her future research.

The next steps, she says, will be to look at how the brain can sense other compounds to regulate not only liver secretion of fats, but also liver glucose production, a significant contributing factor to diabetes. As a member of the Group on Molecular and Cell Biology of Lipids and with the strength of the ADI, she feels enthusiastic and inspired by her new research environment at the University of Alberta.

"It's a big field and it's emerging," says Yue about neuroscience research in the areas of metabolic disease. "Whereas the peripheral organs have gained a lot of attention in terms of how they release glucose and lipids, it's exciting to see that within the last decade and a half that the brain now is emerging as an organ that has a lot of control over our health."