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URMC / Obstetrics & Gynecology / UR Medicine Menopause and Women's Health / menoPAUSE Blog / November 2021 / My doctor always cautions me about my cholesterol, but triglycerides are on the list in my medical r

My doctor always cautions me about my cholesterol, but triglycerides are on the list in my medical record. Can you explain what they do?

Your Menopause Question: My doctor always cautions me about my cholesterol. Occasionally, we even get into a discussion about low-density lipoprotein (LDL) and high-density lipoprotein (HDL), but triglycerides are on the list in my medical record. Can you explain what they do?

Our Response: For many people, the story of lipids in our bodies is confusing. Often heard in the primary care office is the following, “Your cholesterol and triglycerides are too high and introduce a cardiovascular risk” (Harchaoui, 2009, and Kumar, 2016). What is left out of that discussion is that the family of lipids are essential for our bodies’ health. For example, cholesterol is critical for maintaining permeability and fluid dynamics across cell membranes. Because cholesterol as a lipid cannot exist in blood alone, it requires a transport system. Low-density lipoprotein delivers cholesterol to the liver, while HDL removes cholesterol to be excreted (Botham, 2012). However, when we speak about how our cells expend energy, the conversation shifts. How do fatty acids, extracted from the food we eat, end up as fuel for our muscles and fat? And, what is cell energy expenditure anyhow?

Triglycerides are the main constituent of animal and vegetable fats in dietary foods like oil, margarine, and butter. The correct name for triglycerides is triacylglycerol, whose purpose is to provide energy for our cells. Triacylglycerol forms when three hydroxyl groups from a glycerol molecule react with a carboxyl group (-COOH) of fatty acids to form ester bonds. (Are you glad you asked?) Moreover, triacylglycerol consists of two main fats, saturated and unsaturated fats. Most animal fats are saturated fats, while most vegetable fats are unsaturated fats. This is why not all triglycerides are the same (Harchaoui, 2009).

Where do triglycerides originate? We have to go back to the beginning, in the intestine. Bile salts in the lumen of our intestine allow the emulsification (mixing of fat and water) of dietary triglycerides and cholesterol that, in turn, are modified by lipid lipases to produce free fatty acids and monoacylglycerides. Pancreatic lipases then hydrolyze (break down) the ester bonds to release the fatty acids.

Like cholesterol, triglycerides are insoluble in plasma, so they must use a transport carrier system to reach muscle or adipose tissue. This carrier system relies on lipoproteins. So what are these lipoproteins? There are four major lipoprotein particles: chylomicrons (CMs), very low-density lipoproteins, low-density lipoproteins, and high-density lipoproteins. Triglycerides are packaged in these lipoproteins, which are the major carrier systems in the blood, and they are transported to muscle or fat.

So, let’s go back to the intestine. Lipid digestion begins with chylomicrons. Chylomicrons are large, triglyceride–rich lipoproteins produced in cells (called enterocytes) that are located in the intestinal lining. They have a central core, 75% of which consists of triglycerides, but that also can transport cholesterol and other phospholipids. Chylomicrons leave the intestine and enter the systemic circulation where fatty acids are cleaved off to be available for energy. Once triglycerides are removed, the chylomicron remnants, made up mostly of cholesterol, are taken up by the liver.

So, how does all this help cells to use fuel for energy? Triacylglycerols are downgraded to fatty acids and glycerol from the adipose tissue and transported to energy-requiring tissues (Berg, 2002) There, the fatty acids must be activated and transported into mitochondria within cells where the actual energy is produced. The fatty acids are broken down by a series of steps into acetyl CoA, which is processed into the citric acid cycle to form adenosine triphosphate (ATP) (Dunn, 2021). Adenosine triphosphate is hydrolyzed (the process by which a substance is broken down, either by adding or taking away water) to release the bonds of two of the three phosphate groups. This process of ATP production can increase or decrease, depending on the tissue needs. Energy from ATP now is believed to result as water molecules are pulled away, which breaks the molecular bridges between components of ATP (Parke, 2010).

From this discussion, it is safe to say that despite decades of research on lipid metabolism and its relationship to cardiovascular health, the field is still in its infancy. Scientists have come a long way in creating the building blocks, but the real answers to cardiovascular risk will come when studies at a molecular and cellular level produce new therapies to protect heart health.

James Woods | 11/25/2021

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