Diacylglycerols (DAGs) are a class of lipid molecules found throughout the biological world. They are components of cellular membranes and serve as intermediates in metabolic pathways. As naturally occurring components in many oils and as signaling molecules within our cells, diacylglycerols have a dual role in both energy metabolism and cellular communication, making them an area of ongoing scientific inquiry.
Understanding Diacylglycerol Structure
A diacylglycerol molecule consists of a central glycerol backbone to which two fatty acid chains are attached through stable ester bonds. The “di-” in diacylglycerol signifies the presence of these two fatty acid chains. This framework allows for significant variation, as the identity of a specific DAG is determined by the length and saturation of its two fatty acid chains. This structural diversity allows different DAGs to have distinct physical properties and biological functions.
The structure of diacylglycerol is often compared to that of triglycerides, which have three fatty acid chains, and monoglycerides, which have only one. Another structural aspect is the position of the fatty acids on the glycerol molecule. This leads to isomers like 1,2-diacylglycerol and 1,3-diacylglycerol, which participate in different metabolic pathways.
Metabolic Pathways of Diacylglycerols
The concentration of diacylglycerols within a cell is governed by a balance of synthesis and breakdown pathways. One route of DAG production is through the breakdown of triglycerides, the body’s primary energy storage molecules. Enzymes known as lipases cleave one fatty acid from a triglyceride molecule in a process called hydrolysis, resulting in diacylglycerol formation. This occurs during the digestion of fats and within cells to mobilize stored energy.
Another pathway for DAG synthesis is linked to cellular communication. Enzymes called phospholipase C (PLC) act on specific membrane lipids known as phospholipids. PLC cleaves a molecule named phosphatidylinositol 4,5-bisphosphate (PIP2), generating two new molecules: diacylglycerol and inositol 1,4,5-trisphosphate (IP3). The newly formed DAG remains embedded within the membrane, ready to perform its signaling duties.
Once produced, a diacylglycerol molecule does not persist for long. One fate for DAG is to be phosphorylated by an enzyme called diacylglycerol kinase (DGK), which adds a phosphate group to create phosphatidic acid. Alternatively, DAG can be converted back into a triglyceride for energy storage through acylation by the enzyme diacylglycerol acyltransferase (DGAT).
Diacylglycerols as Cellular Messengers
Beyond their role in metabolism, diacylglycerols function as second messengers, which are small molecules that transmit signals from the cell surface to targets within the cell. When a hormone or neurotransmitter binds to a receptor, it can trigger the enzymatic production of DAG within the plasma membrane. Because DAG is a hydrophobic lipid, it remains localized to the membrane, where it can interact with specific target proteins.
The most well-documented function of DAG as a second messenger is the activation of enzymes called Protein Kinase C (PKC). After its generation, DAG recruits PKC from the cell’s cytoplasm to the plasma membrane. The binding of DAG to a specific region on the PKC molecule, the C1 domain, causes a conformational change in the enzyme, switching it to its active state.
Once activated, PKC can influence a wide array of cellular activities by phosphorylating other proteins. This addition of a phosphate group acts like a molecular switch, altering the function of the target proteins. The cellular processes regulated by the DAG-PKC signaling axis include:
- Cell growth
- Proliferation
- Differentiation
- Programmed cell death (apoptosis)
Dietary Diacylglycerols and Health
Diacylglycerols are present not only within our cells but also in the foods we eat as a minor component of many natural vegetable oils. In addition to these amounts, specialized DAG-rich oils have been manufactured and marketed for their potential health benefits. These oils differ from conventional cooking oils, which are composed almost entirely of triglycerides, in their metabolic fate after consumption.
Research suggests that dietary DAGs, particularly the 1,3-DAG isomer, are processed differently in the gut than triglycerides. This distinct metabolic pathway may lead to an increase in fat oxidation and a decrease in the amount of fat that is re-synthesized and stored in the body. Some clinical studies show that replacing conventional oils with DAG oil can lead to modest reductions in body weight, visceral fat, and waist circumference. Other studies have reported lower post-meal triglyceride levels in the blood.
The use of manufactured DAG oils has been accompanied by safety discussions. Around 2009, concerns were raised when it was discovered that some DAG oils contained higher levels of contaminants known as glycidyl fatty acid esters (GEs) from high-temperature industrial processing. The free form of glycidol is considered a potential carcinogen, which prompted some manufacturers to voluntarily halt sales. However, subsequent research has suggested the amount of glycidol released in the body is likely negligible, and newer formulations have been developed and tested for safety.