Lipidomics
Lipidomics is a specialized field of study focused on the structure and function of lipids in living organisms. Lipids, which include substances like oils, fats, steroids, and waxes, are organic compounds that do not dissolve easily in water. These molecules play vital roles in the body, from energy storage to facilitating communication between cells. The term "lipidomics" arose in the early twenty-first century as scientists embarked on a comprehensive effort to identify and classify the complex array of lipids present in biological systems.
Research in lipidomics has revealed a wide variety of lipid classes, including fatty acids, glycerolipids, and sterol lipids, each with unique chemical structures and functions. Notably, lipidomics has provided insights into important medical conditions such as Alzheimer’s disease, theorizing that certain lipids may influence the formation of protein clumps in the brain associated with this condition. Additionally, emerging studies suggest that protecting the blood-brain barrier could be crucial for preventing Alzheimer's. Overall, lipidomics is a burgeoning area of research that promises to enhance our understanding of health and disease through the lens of lipid function.
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Subject Terms
Lipidomics
Lipidomics is the study of the structure and function of lipids in living organisms. Lipids are organic compounds that do not dissolve easily in water. They may include oils, waxes, steroids, and fats. The name lipid comes from the Greek word lipos, meaning "animal fat." Lipids perform a variety of functions in the body, from storing energy to delivering chemical messages between cells. However, their complex natures have made them more difficult to categorize than other organic structures. In the early twenty-first century, scientists began a decade-long study to identify and classify the lipids in living organisms. The new field resulting from the research became known as lipidomics.
Background
The scientific study of living organisms can be divided into classifications based on specific aspects of molecular biology. The study of these fields is often designated by the suffix -ome, meaning the "total" accumulation of knowledge on the subject. The genome is the complete set of genetic instructions found in an organism's DNA (deoxyribonucleic acid). The body decodes sequences of DNA to create genes. These carry specific instructions that control hereditary traits and how some systems in the body function. In the early 1990s, scientists began a project to map and identify the entire DNA sequence of the human genome. The $2.7 billion project was completed in 2003.
The transcriptome refers to the total set of RNA (ribonucleic acid) molecules produced by the genome. RNA acts as a messenger, carrying the genetic instructions, or "transcripts," from the DNA to the body. The proteome is the complete set of proteins in an organism. Proteins are organic molecules that perform many vital functions in the body. The metabolome is the total number of small organic chemical molecules that aid or are produced by the body's metabolism. The metabolome includes organic compounds such as amino acids, nucleotides, sugars, and lipids.
Overview
While the study of the genome was a complicated and expensive process, the knowledge scientists gained from the research allowed them insight into other features of molecular biology. DNA instructions may contain billions of genetic sequences, but those sequences exhibited predicable patterns that significantly aided the study of the transcriptome and proteome. The lipidome—the total number of lipids in an organism—proved much more difficult to understand.
The common characteristic of lipids is that they are hydrophobic, meaning they do not mix well with water. Apart from that, some lipids—such as fats and waxes—contain two chemical components, while others contain three or more. Some lipids even have segments that exhibit hydrophilic properties—the ability to mix well with water.
In 2003, Edward Dennis, a biochemistry professor at the University of California in San Diego, received funding from the National Institutes of Health (NIH) to begin the first study of the lipidome—the Lipid Metabolites and Pathways Strategy (Lipid MAPS). The project ran into trouble almost immediately when it was discovered there was no common classification system in place to handle any research results. The researchers standardized lipid classification into eight categories—fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides—and developed a common system for illustrating their structures.
The Lipid MAPS project was conducted at six laboratories and lasted for a decade at a cost of $73 million. Researchers at each lab used a liquid chromatography–mass spectrometry system to isolate and identify specific lipids. The data from the labs was then analyzed to complete a profile of each lipid. By the time the project was completed, researchers had amassed a database of more than forty thousand lipids.
The eight categories of lipids are divided based on their chemical structure. Fatty acids are simple organic molecules consisting of carboxylic acid (chemical formula COOH) and a long chain of hydrogen and carbon atoms. Most have an even number of carbon atoms that typically range between twelve and twenty. If the carbon atoms in the hydrocarbon chain are joined together by a single bond—two atoms sharing one pair of electrons—the carbon atoms can attach more freely with the hydrogen atoms. Fatty acids of this type are known as saturated, meaning the lipid is "saturated" with hydrogen. If the carbon atoms are connected by a double bond—sharing two pairs of electrons—less carbon electrons are free to join with hydrogen and the fatty acid is said to be unsaturated.
Glycerolipids are formed by joining fatty acids with glycerol, a liquid organic compound often used as a sweetener. One of the most common types of glycerolipids is triglycerides, the main substance that makes up body fat in humans and other mammals. Triglycerides are formed through the bonding of glycerol with three fatty acids. After a person eats, excess calories are converted into triglycerides, which are stored in fat cells. Triglycerides store energy that can be used by the body between meals. If a person eats more than his or her body needs, an excess amount of triglycerides can accumulate in increased fat content. Because lipids do not dissolve in the blood, an increased amount of triglycerides in the bloodstream may raise the risk of heart disease.
Glycerophospholipids are more commonly referred to as phospholipids. These lipids are formed from glycerol, two fatty acids, and a phosphate group—a phosphorus atom bonded with four oxygen atoms. Phospholipids make up the thin membranes that surround and protect the interior of cells. Phospholipid molecules have two ends—a head and a tail. The tail end consists of the two hydrocarbon fatty acid chains. The head contains the phosphate group and is able to mix with water molecules. The membrane of a cell is arranged in a double layer of phospholipids, with the tails facing in toward each other. Because water is common both outside and inside the cell, the phospholipid heads are always exposed to the water while the tails are shielded.
Sphingolipids are also found in the membranes of plant and animal cells. These lipids are formed from long chains of fatty acids and sphingosine, an amino alcohol—organic compounds with properties of both alcohol and amine. Alcohol is an organic compound in which an oxygen-hydrogen molecule is bonded to a saturated carbon atom. An amine is a compound derived from ammonia. Sphingolipids in the skin play a role in keeping the body's water from seeping out through the skin.
Sterol lipids are a naturally occurring type of steroid. Steroids are organic compounds with a core molecular structure of four fused rings of carbon atoms. Steroids perform various functions in the body. Some trigger chemical responses that act as signaling mechanisms between cells; others are found in cell membranes and make the membrane more fluid. One of the most common steroids is cholesterol, a compound that helps produce vitamin D and the sex hormones testosterone and estradiol. Cholesterol is typically produced by the liver, but its levels can be affected by diet. A diet high in saturated fats can lead to more cholesterol in the blood; a diet high in unsaturated fats can lower blood cholesterol. For this reason, people with a higher risk of heart disease are often advised to cut down on foods with high saturated fat content.
Prenol lipids are naturally occurring alcohols. They are found in oils present in orange peels and other fruits, including limes, grapes, and pineapples. Prenol lipids also play a role in the formation of vitamins A, E, and K. Saccharolipids are compounds in which fatty acids are linked to the chemical framework of a sugar. Sugars are carbohydrates, which are chemical compounds formed from carbon, hydrogen, and oxygen. Some saccharolipids can be formed from glucosamine, a natural sugar found in the body. Glucosamine is often used as a dietary supplement. Polyketides are complex lipids that are not produced to directly aid in the metabolic growth of an organism. They are often produced as a survival mechanism. Certain toxins found in fungi are examples of polyketides.
Despite being a relatively new field, lipidomics has led to a number of medical advancements, including new insight into the cause and treatment of Alzheimer's disease. Alzheimer's is a progressive disease that destroys a person's memory and other brain functions. The exact cause of Alzheimer's disease is unknown, but scientists believe a buildup of sticky protein clumps, or plaques, in the brain may play a significant role in the disease. Scientists have discovered that a protein linked to Alzheimer's is also a primary transporter of lipids in the body. Certain lipids have also been found to reverse the process that forms the protein plaques, leading to speculation that lipids may help in finding a cure for Alzheimer's disease. A 2023 article in the Journal of Alzheimer's Disease revealed a potential breakthrough in understanding the disease. Called the Lipid Invasion Model (LIM), it purports that lipids invade the brain because the blood-brain barrier (BBB) has been damaged. According to the study, researchers believed that protecting and repairing the BBB may be a key to preventing the development of Alzheimer's disease.
Bibliography
Dove, Alan. "Greasing the Wheels of Lipidomics." Science, 13 Feb. 2015, www.sciencemag.org/features/2015/02/greasing-wheels-lipidomics. Accessed 7 Mar. 2018.
Furse, Samuel. "The Lipid Chronicles." The Lipid Chronicles, www.samuelfurse.com/lipids/. Accessed 7 Mar. 2018.
Goldberg, Anne Carol. "Overview of Cholesterol and Lipid Disorders." Merck Manual, www.merckmanuals.com/home/hormonal-and-metabolic-disorders/cholesterol-disorders/overview-of-cholesterol-and-lipid-disorders. Accessed 7 Mar. 2018.
"Human Genome Project." National Institutes of Health, 29 Mar. 2013, report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=45&key=H#H. Accessed 7 Mar. 2018.
Leray, Claude. Introduction to Lipidomics: From Bacteria to Man. CRC Press, 2013.
"Lipids." OpenStax CNX, cnx.org/contents/GFy‗h8cu@9.85:I‗8zQ2kk@8/Lipids. Accessed 7 Mar. 2018.
Proitsi, Petroula, et al. "Association of Blood Lipids with Alzheimer's Disease: A Comprehensive Lipidomics Analysis." Alzheimer's & Dementia, Feb. 2017, www.alzheimersanddementia.com/article/S1552-5260(16)30022-X/fulltext. Accessed 7 Mar. 2018.
Rudge, Jonathan D'Arcy. "The Lipid Invasion Model: Growing Evidence for This New Explanation of Alzheimer's Disease." Journal of Alzheimer's Disease, vol. 94, no. 2, 18 July 2023, pp. 457-470, DOI: 10.3233/JAD-22117. Accessed 9 Nov. 2024.
Swinnen, Johannes V., and Dehairs, Jonas. "A Beginner's Guide to Lipidomics." Biochem, 2022, doi.org/10.1042/bio‗2021‗181. Accessed 7 Nov. 2024.
"The Three Classifications of Lipids Found in Food and in the Human Body." San Francisco Chronicle, healthyeating.sfgate.com/three-classifications-lipids-found-food-human-body-11865.html. Accessed 7 Mar. 2018.
"Tutorials and Lectures on Lipids." Lipid MAPS, www.lipidmaps.org/resources/tutorials/lipid‗tutorial.html. Accessed 7 Mar. 2018.