Common Dietary Fat and Intestinal Microbes Linked to Heart Disease

Common Dietary Fat and Intestinal Microbes Linked to Heart Disease

  12:22:00 PM    Science Lover

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A new pathway has been discovered that links a common dietary lipid and intestinal microflora with an increased risk of heart disease, according to a Cleveland Clinic study published in the latest issue of Nature.

Baked goods. Lecithin, and its metabolite, choline, are found in many commercial baked goods, dietary supplements, and even children's vitamins, as well as eggs, liver and other meats, cheese and other dairy products, fish and shellfish. (Credit: iStockphoto)

The study shows that people who eat a diet containing a common nutrient found in animal products (such as eggs, liver and other meats, cheese and other dairy products, fish, shellfish) are not predisposed to cardiovascular disease solely on their genetic make-up, but rather, how the micro-organisms that live in our digestive tracts metabolize a specific lipid -- phosphatidyl choline (also called lecithin). Lecithin and its metabolite, choline, are also found in many commercial baked goods, dietary supplements, and even children's vitamins.

The study examined clinical data from 1,875 patients who were referred for cardiac evaluation, as well as plasma samples from mice. When fed to mice, lecithin and choline were converted to a heart disease-forming product by the intestinal microbes, which promoted fatty plaque deposits to form within arteries (atherosclerosis); in humans, higher blood levels of choline and the heart disease forming microorganism products are strongly associated with increased cardiovascular disease risk.

"When two people both eat a similar diet but one gets heart disease and the other doesn't, we currently think the cardiac disease develops because of their genetic differences; but our studies show that is only a part of the equation," said Stanley Hazen, M.D., Ph.D., Staff in Lerner Research Institute's Department of Cell Biology and the Heart and Vascular Institute's Department of Cardiovascular Medicine and Section Head of Preventive Cardiology & Rehabilitation at Cleveland Clinic, and senior author of the study. "Actually, differences in gut flora metabolism of the diet from one person to another appear to have a big effect on whether one develops heart disease. Gut flora is a filter for our largest environmental exposure -- what we eat."



Dr. Hazen added, "Another remarkable finding is that choline -- a natural semi-essential vitamin -- when taken in excess, promoted atherosclerotic heart disease. Over the past few years we have seen a huge increase in the addition of choline into multi-vitamins -- even in those marketed to our children -- yet it is this same substance that our study shows the gut flora can convert into something that has a direct, negative impact on heart disease risk by forming an atherosclerosis-causing by-product."

In studies of more than 2,000 subjects altogether, blood levels of three metabolites of the dietary lipid lecithin were shown to strongly predict risk for cardiovascular disease: choline (a B-complex vitamin), trimethylamine N-oxide (TMAO, a product that requires gut flora to be produced and is derived from the choline group of the lipid) and betaine (a metabolite of choline).

"The studies identify TMAO as a blood test that can be used in subjects to see who is especially at risk for cardiac disease, and in need of more strict dietary intervention to lower their cardiac risk," Dr. Hazen said.

Healthy amounts of choline, betaine and TMAO are found in many fruits, vegetables and fish. These three metabolites are commonly marketed as direct-to-consumer supplements, supposedly offering increased brain health, weight loss and/or muscle growth.

These compounds also are commonly used as feed additives for cattle, poultry or fish because they may make muscle grow faster; whether muscle from such livestock have higher levels of these compounds remains unknown.

"Knowing that gut flora generates a pro-atherosclerotic metabolite from a common dietary lipid opens up new opportunities for improved diagnostics, prevention and treatment of heart disease," Dr. Hazen said. "These studies suggest we can intelligently design a heart healthy yogurt or other form of probiotic for preventing heart disease in the future. It also appears there is a need for considering the risk vs. benefits of some commonly used supplements."

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Scientists Create Cell Assembly Line: New Technology Synthesizes Cellular Structures from Simple Starting Materials

Scientists Create Cell Assembly Line: New Technology Synthesizes Cellular Structures from Simple Starting Materials

  12:29:00 AM    Science Lover

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Borrowing a page from modern manufacturing, scientists from the Florida campus of The Scripps Research Institute have built a microscopic assembly line that mass produces synthetic cell-like compartments.

Artist's rendering of cell structure. 
(Credit: iStockphoto/Sebastian Kaulitzki)

 

The new computer-controlled system represents a technological leap forward in the race to create the complex membrane structures of biological cells from simple chemical starting materials.

"Biology is full of synthetic targets that have inspired chemists for more than a century," said Brian Paegel, Scripps Research assistant professor and lead author of a new study published in the Journal of the American Chemical Society. "The lipid membrane assemblies of cells and their organelles pose a daunting challenge to the chemist who wants to synthesize these structures with the same rational approaches used in the preparation of small molecules."

While most cellular components such as genes or proteins are easily prepared in the laboratory, little has been done to develop a method of synthesizing cell membranes in a uniform, automated way. Current approaches are capricious in nature, yielding complex mixtures of products and inefficient cargo loading into the resultant cell-like structures.

The new technology transforms the previously difficult synthesis of cell membranes into a controlled process, customizable over a range of cell sizes, and highly efficient in terms of cargo encapsulation.

The membrane that surrounds all cells, organelles and vesicles -- small subcellular compartments -- consists of a phospholipid bilayer that serves as a barrier, separating an internal space from the external medium.

The new process creates a laboratory version of this bilayer that is formed into small, cell-sized compartments.

How It Works

"The assembly-line process is simple and, from a chemistry standpoint, mechanistically clear," said Sandro Matosevic, research associate and co-author of the study.

A microfluidic circuit generates water droplets in lipid-containing oil. The lipid-coated droplets travel down one branch of a Y-shaped circuit and merge with a second water stream at the Y-junction. The combined flows of droplets in oil and water travel in parallel streams toward a triangular guidepost.

Then, the triangular guide diverts the lipid-coated droplets into the parallel water stream as a wing dam might divert a line of small boats into another part of a river. As the droplets cross the oil-water interface, a second layer of lipids deposits on the droplet, forming a bilayer.

The end result is a continuous stream of uniformly shaped cell-like compartments.

The newly created vesicles range from 20 to 70 micrometers in diameter -- from about the size of a skin cell to that of a human hair. The entire circuit fits on a glass chip roughly the size of a poker chip.

The researchers also tested the synthetic bilayers for their ability to house a prototypical membrane protein. The proteins correctly inserted into the synthetic membrane, proving that they resemble membranes found in biological cells.

"Membranes and compartmentalization are ubiquitous themes in biology," noted Paegel. "We are constructing these synthetic systems to understand why compartmentalized chemistry is a hallmark of life, and how it might be leveraged in therapeutic delivery."

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