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.

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Source: NIH, National Institute of General Medical Sciences (NIGMS)