Mysterious Fats Fuel Disease More Than We Knew, New Research Reveals
New technologies detect thousands of different fats throughout the human body that predict disease and determine health
A deadly contaminant stopped thousands of people’s hearts, resulting in their deaths, but nobody knew why. Then, in the 1950s, biochemist Fred Kummerow scraped open their arteries and found a lethal fat that had come from their food. As he learned, different fats in our diet are the determinants of health and disease, and control who lives and who doesn’t.
“It’s simple, if it jiggles, it’s fat,” Arnold Schwarzenegger once said. How wrong he was. Yes, there are everyday fats like cooking oils, lard, and heavy cream. These are just the tip of the fat iceberg, as recent science has shown.
The heart attacks Kummerow studied were caused by a specific fat in processed foods, just one of many fatty molecules. But now another deep and enduring mystery has scientists scratching their heads: Why does Nature use thousands of fat molecules, when a small number should suffice?
A new generation of ultrasensitive chemistry technologies has indeed discovered thousands of rapidly shifting fat molecules in the human body that impact nearly all aspects of health. Tracking changes in these fatty molecules predicts future onset of a wide variety of diseases, from heart, brain, and liver diseases to infectious diseases, organ failure, and many cancers, and offers radically new treatment approaches using both diet and drugs.
The heart attack victims had clogged arteries, Fred Kummerow found after examining more than 20 people who died of heart attacks. Trans fats were the culprits — he found vessels clogged with this fat, which is abundant in processed foods. He concluded that thousands of people die from trans fats each year and launched a campaign to ban these fats, which was finally implemented in 2018, 70 years after his first observation.
Many fats hurt your health because they clog your arteries and damage your organs, such as your liver and brain:
- Trans fats cause deadly heart attacks by blocking blood flow to the heart; they are now illegal due to the work of Kummerow.
- Cholesterol, a fatty molecule, increases heart attack risk, also by clogging arteries — the commonly used statin drugs work by reducing cholesterol in the body.
- Saturated fats cause liver damage, brain damage, and heart attacks by clogging arteries and directly damaging these organs.
- Some fats with complex names reduced to acronyms, such as DGLA, cause brain diseases by killing specific brain cells, such as the ones lost in Parkinson’s Disease, a recent study found
Deadly fats can be categorized based on their chemical structures, and the damage they do. Trans fats, saturated fats, and DGLA have similar pencil-like, long and thin chemical structures, whereas cholesterol looks quite different, more like a series of keyrings strung together. But both kinds of fats are dangerous.
The healthy fats
Healthy hearts and brains require fat molecules with beneficial effects, such as omega-3 fatty acids found in fish. These omega-3 fatty acids have the long pencil-like shape like some of the deadly fats, but with a few kinks, and help the brain and heart function well by dampening an overactive immune system.
Health and longevity are also associated with another fat present in olive oil, which is linked to long life and vitality. In the movie Lorenzo’s Oil, a 5-year-old boy develops a devastating brain disease due to deficiency in healthy fats essential for developing kids.
Oily molecules such as cholesterol and trans fats are called lipids — derived from the Greek word lipos for fat or grease. Unlike most molecules, lipids avoid water and stick in the greasy membranes surrounding cells.
Mapping the world of fatty lipids
DNA and genes are the subject of a vast number of studies. Lipids not so much. Nonetheless, researchers have detected a growing number of lipids in the decades since Kummerow made his discovery about trans fats.
Impressive advances in chemistry detectors have dramatically improved the ability to measure many different lipids in human cells and tissues. Indeed, a single human cell has thousands of distinct lipids, each with a different function and role in health and disease.
A new field of science has sprung up around this technology for detecting lipids, known as lipidomics. Researchers in this new and growing field use sophisticated instruments to measure the amounts of each of thousands of lipids in different cells and different parts of the body.
COVID-19 and other patients with infectious diseases harbor specific lipids. A recent study used lipidomics technology to measure the amounts of thousands of lipids in such patients and found a group of lipids called PEs are elevated in patients with persistent illness; high amounts of PEs predict more severe disease.
PEs are specialized lipids that help form the barrier around cells. Their full formal name is phosphatidyl-ethanol-amines, because they are composed of three pieces—a phosphatidyl group (similar to chemicals in some laundry detergents), an ethanol group (the same molecule found in alcoholic drinks) and an amine, similar to the cleaning product ammonia. When you put these together, you get the PE lipid.
Who will live and who will die? The answer may be found in elevated PEs after infection. This study provided a new way to predict which patients will get better and which will face long-term illness. This information is crucial in determining when and how to treat patients.
This year, Nestor Cortes, a pitcher for the New York Yankees, suffered a rotator cuff injury, which took him out for the season. While we don’t know the details of his specific injury, rotator cuff injuries were associated with elevated PE lipids in a recent study. The rotator cuff consists of muscles around the shoulder joint that keep the arm bone in the shoulder socket. Injury to the rotator cuff causes pain in the shoulder and is common in sports such as baseball. Being able to predict who is likely to suffer this injury could help prevent it, and might have kept the Yankees in contention.
The mystery of lipid complexity and exploding cells
Why so many lipids? Different lipids may control how stretchy and durable cell membranes are. Some membranes are stiffer and others are soft and stretchy. These properties affect how cells interact with each other and how molecules within membranes behave.
Cells can even explode when their lipids react with oxygen. Some lipids, such as the ones that make membrane stretchy, are particularly prone to such reactions. Having too many of these lipids in a membrane can act as a fuse, potentially causing a cell explosion.
The huge untapped resource of lipid biology holds the key to predicting and treating a vast number of diseases. However, the true function of each of the thousands of lipids remains largely unknown, and will require years of study to determine.
Former President Bill Clinton twice had surgery to bypass arteries clogged with fat, after eating fatty fast foods most of life. “I was lucky I didn’t die of a heart attack,” he told Dr. Sanjay Gupta of CNN in 2004. Clinton made a radical switch to a vegan diet, which is low in saturated fat and better for his heart. Best we know, he has been healthy ever since. As Clinton learned, the fats in our diet can indeed be the difference between life and death.
We are on the cusp of a revolution in lipidomic biology driven by this new technology, which continues to advance rapidly. Predicting how lipidomics technology will change healthcare and medicine over the next decade is difficult because the potential is so vast.
We’re using this powerful new technology in my lab at Columbia University to understand which lipids control cell survival, and how we can create new diets and medicines to prevent disease. After all, as computer scientist Alan Kay said, “The best way to predict the future is to invent it.”
