Lipids are fat-like substances that are important parts of the membranes found within and between cells and in the myelin sheath that coats and protects the nerves. Lipids include oils, fatty acids, waxes, steroids (such as cholesterol and estrogen), and other related compounds.

These fatty materials are stored naturally in the body’s cells, organs, and tissues. Tiny bodies within cells called lysosomes regularly convert, or metabolize, the lipids and proteins into smaller components to provide energy for the body. Disorders in which intracellular material that cannot be metabolized is stored in the lysosomes are called lysosomal storage diseases. In addition to lipid storage diseases, other lysosomal storage diseases include the mucolipidoses, in which excessive amounts of lipids with attached sugar molecules are stored in the cells and tissues, and the mucopolysaccharidoses, in which excessive amounts of large, complicated sugar molecules are stored.

When you have your cholesterol checked, the doctor typically provides your levels of three fats found in the blood: LDL, HDL and triglycerides. But did you know your body contains thousands of other types of fats, or lipids?

In human plasma alone, researchers have identified some 600 different types relevant to our health. Many lipids are also associated with diseases-diabetes, stroke, cancer, arthritis, Alzheimer's disease, to name a few. Learning more about them could point to new ways to diagnose and treat lipid-related conditions.

Lipid Encyclopedia

Just as genomics and proteomics spurred advances in the study of genes and proteins, lipidomics has offered a more quantitative and systematic approach to lipids research. Much of the effort has been led by a research consortium called LIPID MAPS. With funding from the National Institutes of Health, LIPID MAPS' first major activity was classifying lipids into eight main categories. Six include fats from mammals and the other two include fats from bacteria, plants and marine life. Cholesterol belongs to the "sterol" group, and triglycerides are "glycerolipids." Another category, "phospholipids," includes the hundreds of lipids that constitute the cell membrane and allow cells to send and receive signals.

Aside from describing more than 35,000 lipids and providing details about them via an open database, the scientists have found ways to make these oily substances easier for others to work with. This includes improving the ability to separate, quantify and analyze lipids from urine, blood, phlegm and biopsied tissue.

The overall effort has now made it possible to study how lipids change and interact over time. For example, by tracking the activity of about 500 fat species in mouse white blood cells, the LIPID MAPS scientists could measure hour-by-hour changes in lipid levels after the cells were exposed to an infection-fighting trigger—a bacterial endotoxin—and began to experience inflammation. They also studied what happened to lipid levels after the cells were exposed to a statin drug, which blocks cholesterol production, and after exposure to both the endotoxin and a statin.

The scientists observed some expected trends, like a reduction in cholesterol after exposure to a statin drug, but they noticed some surprising ones, too. Because statins also can reduce inflammation, the researchers expected to see fewer prostaglandins, which are inflammation-producing hormones made from lipids; instead, they saw an increase. While the scientists aren't yet sure why this happened, they have begun to produce a picture of lipid dynamics that could set the stage for a better understanding of these dynamics in human cells.

Lipid Mechanics

Another important question about lipids is how they work. If scientists can make an artificial cell membrane for their lab studies using only a few lipids, then why do real membranes need thousands? LDL brings cholesterol to a cell and HDL removes it, but what are the underlying mechanisms? Cod liver oil has been touted as a treatment for eczema, arthritis and heart disease for decades, but how does its active ingredient—a lipid called an omega-3 fatty acid—actually operate?

Using the lipidomics data and tools, members of LIPID MAPS have answered this last question.

Once again using mouse white blood cells, the scientists gave the cells supplements of pure fatty acids (fish oil is a mixture). These included eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-both polyunsaturated omega-3s. And as in the earlier study, they stimulated an immune response, including inflammation.

But these cells didn't display the typical response. Instead, EPA and DHA blocked the activity of an enzyme called COX, which helps convert an omega-6 fatty acid into inflammatory prostaglandins. Inflammation is a common element of many diseases, so understanding how omega-3 fatty acids could stem it has tremendous therapeutic potential.

This knowledge is just the tip of the fat-filled iceberg. We've already learned a lot about lipids, but much more remains to be discovered.

By Emily Carlson

You’ve probably heard about different types of fat, such as saturated, trans, monounsaturated, omega-3, and omega-6. But fats aren’t just ingredients in food. Along with similar molecules, they fall under the broad term lipids and serve critical roles in the body. Lipids protect your vital organs. They help cells communicate. They launch chemical reactions needed for growth, immune function, and reproduction. They serve as the building blocks of your sex hormones (estrogen and testosterone).

Here we feature five of the hundreds of lipids that are essential to health.

Docosahexaenoic Acid (DHA)

DHA is an omega-3 fatty acid (known nutritionally as a “good” fat). It makes up a significant portion of the human brain, skin, sperm, testicles, and retina (part of the eye).

Although our bodies can make very small amounts of DHA, the most common source of DHA is food. Fish and seafood, particularly fatty cold-water fish such as salmon, mackerel, tuna, or herring, are the best places to find this important fat.

Sphingosine-1-Phosphate

Our bodies make sphingosine-1-phosphate by adding a few atoms to another molecule. Although we don’t need much, sphingosine-1-phosphate is necessary throughout the body. It’s especially important for shoring up the walls of blood vessels and allowing only certain molecules to enter and leave the blood stream. It protects the body from disease by directing certain immune cells to locations where they are needed to fight infection. It also has important functions in the brain and nervous system. When sphingosine-1-phosphate signaling goes awry, it can contribute to cardiovascular disease, cancer, or multiple sclerosis.

Retinal

One of many forms of vitamin A, retinal is crucial for our vision. It helps us see under low-light conditions and to recognize colors. The molecule is found in the retina, a thin cell layer at the back of the eyeball. We “see” when light enters our eyes and strikes the retina. There, retinal helps convert the light into a nerve signal. The nerve signal travels to the brain, which forms a visual image. Our bodies can make retinal from other forms of vitamin A, such as carotenes contained in carrots.

2-Arachidonoylglycerol (2AG)

2AG works as a messaging molecule in the brain and in nerve cells throughout the body. Our bodies make it, so we don’t need to get it from food. 2AG belongs to a class of nerve signaling molecules called endocannabinoids, which are similar in structure and function to the active ingredient in cannabis (marijuana). 2AG and the molecules it interacts with affect mood, memory, pain sensation, and appetite. They also are important in fertility and pregnancy. Changes in 2AG levels can contribute to many diseases, such as Alzheimer’s, multiple sclerosis, and atherosclerosis (clogging of blood vessels).

Ursodeoxycholic Acid

Bacteria in our intestines make ursodeoxycholic acid. As starting material, they use molecules known as bile acids that our bodies make in the liver, store in the gall bladder, and secrete into the intestine. Ursodeoxycholic acid helps regulate cholesterol levels. It reduces the rate at which cholesterol enters the blood from the intestine and breaks apart cholesterol clumps. Because of these effects, ursodeoxycholic acid is used as a medication to dissolve gallstones, which are rich in cholesterol. It’s also prescribed to treat certain liver diseases.

By Stephanie Dutchen

It's common knowledge that too much cholesterol and other fats can lead to disease, and that a healthy diet involves watching how much fatty food we eat. However, our bodies need a certain amount of fat to function—and we can't make it from scratch.

Triglycerides, cholesterol and other essential fatty acids—the scientific term for fats the body can't make on its own—store energy, insulate us and protect our vital organs. They act as messengers, helping proteins do their jobs. They also start chemical reactions that help control growth, immune function, reproduction and other aspects of basic metabolism.

The cycle of making, breaking, storing and mobilizing fats is at the core of how humans and all animals regulate their energy. An imbalance in any step can result in disease, including heart disease and diabetes. For instance, having too many triglycerides in our bloodstream raises our risk of clogged arteries, which can lead to heart attack and stroke.

Fats help the body stockpile certain nutrients as well. The so-called "fat-soluble" vitamins—A, D, E and K—are stored in the liver and in fatty tissues.

Knowing that fats play such an important role in many basic functions in the body, researchers funded by the National Institutes of Health study them in humans and other organisms to learn more about normal and abnormal biology.

Looking to Insects for Insight into Fat Regulation

Despite fat's importance, no one yet understands exactly how humans store it and call it into action. In search of insight, Oklahoma State University biochemist Estela Arrese studies triglyceride metabolism in unexpected places: silkworms, fruit flies and mosquitoes.

The main type of fat we consume, triglycerides are especially suited for energy storage because they pack more than twice as much energy as carbohydrates or proteins.

Once triglycerides have been broken down during digestion, they are shipped out to cells through the bloodstream. Some of the fat gets used for energy right away. The rest is stored inside cells in blobs called lipid droplets.

When we need extra energy-for instance, when we run a marathon-our bodies use enzymes called lipases to break down the stored triglycerides. The cell's power plants, mitochondria, can then create more of the body's main energy source: adenosine triphosphate, or ATP.

Arrese works to identify, purify and determine the roles of individual proteins involved in triglyceride metabolism. Her lab was the first to purify the main fat regulation protein in insects, TGL, and now she is trying to learn what it does. She also discovered the function of a key lipid droplet protein called Lsd1, and she is investigating its sister, Lsd2.

Arrese's work could teach us more about disorders like diabetes, obesity and heart disease. Plus, by understanding how insects use fat when they metamorphose and lay eggs and by hypothesizing how to disrupt those processes, her discoveries could lead to new ways for farmers to protect their crops from pests and for health officials to combat mosquito-borne diseases like malaria and West Nile virus.

But before any of that can happen, says Arrese, "We need to study a lot and have information at the molecular level."

Cholesterol and Cell Membranes

One of Arrese's challenges is trying to get oily substances like fat to work in lab tests, which tend to be water-based. However, our cells couldn't function without fat and ?water's mutual dislike.

Cell membranes encase our cells and the organelles inside them. Fat—specifically, cholesterol—makes these membranes possible. The fatty ends of membrane molecules veer away from the water inside and outside cells, while the non-fatty ends gravitate toward it. The molecules spontaneously line up to form a semi-permeable membrane. The result: flexible protective barriers that, like bouncers at a club, only allow the appropriate molecules to cross into and out of cells.

Chew on that the next time you ponder the fate of the fat in a French fry.

Lipid storage diseases, or the lipidoses, are a group of inherited metabolic disorders in which harmful amounts of fatty materials (lipids) accumulate in various cells and tissues in the body. People with these disorders either do not produce enough of one of the enzymes needed to break down (metabolize) lipids or they produce enzymes that do not work properly. Over time, this excessive storage of fats can cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system (the nerves from the spinal cord to the rest of the body), liver, spleen, and bone marrow.