Fats: Structure and Function

Inadvertently, it seems like the macromolecules of life are becoming a series on this blog! A while ago, I made a post about proteins, since they are just so intriguing and critical in biochemistry, as scientists work on proteins to design drugs and study how diseases work. I’ve recently had the opportunity to explore this line of work by finding peptide inhibitors of a particular protein, but that’s a blog post for another time! Anyway, back to fats. In the nutrition world, proteins, fats, and carbohydrates are all well-known for being a critical part of your diet, but fats tend to have a bad reputation as they’re often associated with weight gain. Yet, this link has been questioned lately, and humans have been consuming fat for thousands of years without the epidemic weight gain seen in recent years. But why do we have this connection between fats and weight gain? The story is actually much more complex than you might expect, including a glimpse into how corruption and corporations influence science and can mislead the public for years!

What are the macromolecules of life?

You may have heard of the macromolecules of life: Carbohydrates, lipids, proteins, and nucleic acids. These molecules are responsible for many of the important biological functions in your body, such as providing and storing energy, forming the structures in your body, while the nucleic acids play an important role behind the scenes in encoding for the proteins in your body. In fact, these molecules make up the majority of a cell’s mass! In simple terms, macromolecules are very large molecules that consist of monomers, which are pieces that link together to make up the macromolecule. Carbohydrates are responsible for providing the body’s main source of energy, as it provides a steady source of energy and a quick burst of energy when exercising. However, when the body consumes more carbohydrates than it needs for daily activities, this energy is converted to glucose and stored as fat for long-term storage of energy. This can lead to weight gain if the body consistently stores more fat than it burns off.

First of all, let’s learn about the biochemistry of fat

Out of the macromolecules of life, lipids are characterized by their hydrophobic and nonpolar nature, which means that they are adverse to water molecules. If you’ve ever tried washing off butter or oil using water, you’ll know that lipids are not soluble in water as water is a polar solvent while lipids are nonpolar, although they are soluble in organic solvents such as chloroform. Lipids are typically categorized into fats, phospholipids, waxes, and steroids. 

While the word fat is often used synonymously with lipids, fats are actually lipids that contain a molecule called glycerol with three fatty acids attached. These fatty acids are made up of hydrocarbon tails, and this is what makes the tail end of fats hydrophobic because the carbon-carbon and carbon-hydrogen bonds in the hydrocarbon tail are nonpolar. In fact, fats are often called triglycerides because the structure of fat contains three fatty acids for every glycerol molecule.

Phospholipids are what they sound like – lipids that contain a phosphate group at its hydrophilic, or water-loving, head, and two fatty acids attached at the tail with a glycerol molecule. With the hydrophilic and polar head of the phospholipids, the molecule is arranged with the tails facing inwards and the head facing outwards, which allows it to attract other intracellular and extracellular fluids. Because of their amphipathic nature, meaning they have both hydrophilic and hydrophobic elements, phospholipids are capable of forming a structure called a micelle when placed in water. In this structure, the hydrophilic heads face out in a spherical shape while the hydrophobic fatty acids hide inside the structure, away from the water. This important property allows it to act as a barrier in cellular membranes to protect the cell, and in particular, these types of lipids are responsible for forming myelin on the axons and also found in the brain and nervous tissue.

Waxes, such as beeswax, are esters of long chain alcohols and fatty acids that are produced naturally by plants and animals, often as a protective barrier. However, the exact composition of the wax depends on the species and geographic location of the plant or animal. Waxes are able to provide a protective barrier for the organism because of the hydrophobic nature of lipids that allows for water resistance. For example, you may have noticed that water slides off of the surface of leaves, and this is because the lipids coating the surface of the leaf that protects the plant from dehydration and predators. Outside of natural waxes, synthetic waxes are often made for makeup, polishes, adhesives, food, and other products. For example, the main ingredients of lipstick are wax, oils, and pigments, with the waxes acting as emulsifiers preventing the oils from separating and forming the shape of the lipstick. One synthetic wax that is commonly used to make lipstick, paraffin wax, is made from petroleum, while some other synthetic waxes are made from polyethylene.

Finally, the last category of waxes are steroids. Often associated with drug doping and increasing muscle mass, steroids are categorized as lipids because they are hydrophobic and nonpolar, even though their structure is unlike any other lipid as they have four carbon rings linked together, with some steroids also having a short tail. In steroids containing -OH functional groups, they are called sterols, and this classifies them as alcohols.

The most common steroid is very well-known in the nutrition world – cholesterol. You may have heard about the importance of lowering cholesterol to prevent heart disease and stroke, but a healthy level of cholesterol is actually crucial to your body as it is the precursor to many steroid hormones, including estrogen, testosterone, and progesterone. This steroid is synthesized in the liver, and it serves many functions from helping cells absorb fat to forming the plasma layer that regulates the dynamic of materials within cells, as well as regulating electrical signals in the brain that affects messages from neurotransmitters.

But what about the unhealthy cholesterol that we hear about often? Cholesterol is also in the bloodstream that functions to carry cholesterol throughout the body, and there are two types of cholesterol that function in very different ways. Low-density lipoprotein (LDL) cholesterol transports cholesterol throughout the body, and this is the type of cholesterol that can turn into fatty deposits that clog the blood vessels and cause disease. High-density lipoprotein (HDL) cholesterol picks up excess cholesterol to bring back to the liver, which makes it what people call the “good” cholesterol.

As with the common saying, “the dose makes the poison,” cholesterol isn’t always bad as it’s crucial for the body to build healthy cells, but with high levels of cholesterol caused by consuming too much dietary cholesterol or eating too much saturated or trans fat that causes the liver to synthesize more cholesterol, this can cause fatty deposits to form a thick, hard substance in the arteries that lead to the heart and brain, which causes heart attacks and strokes.

What about the different types of fat?

Besides the categorization of fats based on their structures, fats are also commonly categorized into saturated, unsaturated, and trans fats. Saturated fats are solid at room temperature, and their structure is “saturated” with hydrogens, with a hydrogen atom on every carbon in the hydrocarbon molecule because of the single bond between the carbons. Yet, while saturated fats were commonly known as the “unhealthy” fat because they were known to raise LDL cholesterol levels, here’s where the controversy comes in. Recent studies have been beginning to show that diets high in saturated fat did not raise the risk of heart disease, including a popular and controversial study published in 2014 that stated that there was no evidence that consuming more saturated fat caused an increase in heart attacks. However, this controversy is still being hotly debated by public health experts.

Next, unsaturated fats are liquid at room temperature, and this is because it contains cis unsaturated fatty acids, which means that the configuration of hydrogens around the double bond are in the same plane that prevents the fatty acid from packing tightly due to the bend caused by the cis double bond and turning into a solid at room temperature. Unlike saturated fats, the hydrocarbon chain has double bonds, which reduces the number of hydrogen atoms, so it’s “unsaturated” with hydrogen atoms.

However, the number of double bonds can differ in unsaturated fats. Like its name states, monounsaturated fats have one double bond in the molecule, and some examples of monounsaturated fats include olive oil, canola oil, and sesame oil. Polyunsaturated fats have more than one double bond, and are considered essential fats because they can’t be produced naturally by the body. They include omega-3 fatty acids and omega-6 fatty acids, and some polyunsaturated fats include sunflower oil, corn oil, and soybean oil. Both of these fats are considered to be the “good” fat, and this was because it was found that the people who consumed a Mediterranian diet actually had lower rates of heart disease as the risk of heart disease dropped by 30% in study participants that ate a Mediterranian diet with plenty of olive oil and nuts, both high in unsaturated fat.

Finally, the infamous trans fat. Known for being in all sorts of unhealthy foods – cakes, burgers, fried foods – trans fats can be naturally-occurring or artificial. Some animals, such as cattle, sheep, and goats, naturally produce trans fats in their guts, and small amounts of these trans fats can end up in the food products made from these animals. However, the main source of trans fats in our diets come from the artificially-created trans fat, which occurs in a process called hydrogenation. This process solidifies liquid oils by adding hydrogen atoms, which is like turning unsaturated fats into saturated fats. But why do companies do this? Trans fat has a long shelf-life, is cheap to produce, and also improves the taste and texture of food. Currently, the FDA and American Heart Association have imposed regulations on labeling and recommendations on limiting the quantity of trans fats consumed daily, as it was found that trans fats increases the level of LDL cholesterol and lowers the amount of HDL cholesterol.

“There is insufficient evidence from prospective epidemiologic studies to conclude that dietary saturated fat is associated with an increased risk of CHD, stroke, or CVD.”

Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease, a study that questioned the claim that saturated fat increases risk of heart disease

What is the function of fat?

Yet, despite their bad reputation associated with weight gain, fat is actually incredibly important to the functioning of our bodies. While lipids mainly function to store long-term energy, they also form the structure of cell membranes, messenger, and signalling molecules in the body. When fat is broken down, it can release large amounts of energy as they contain more ATP per molecule at 9 calories per gram compared to 4 calories per gram in carbohydrates. In addition, another important role of fat is to insulate the body. You may have noticed that many animals, particularly animals that live in the arctic and antarctic, have thick layers of blubber protecting their body. This may apply to humans as well, as in a study, it was found that when people who were obese and people who were lean were immersed in cool water, the people with obesity cooled less quickly and did not have to elevate their metabolism to heat up their bodies as much as lean people. This was also shown in the Rottnest Channel Swim in Australia, where participants swim across the 20 kilometer channel in the 70 degree water. In this competition, scientists found that swimmers with a higher body-mass index (BMI) were much less likely to get hypothermia. With fat preventing heat loss, this means that the body doesn’t need to work as hard to stay warm, although an excess of body fat can lead to heat stress in warmer conditions.

Fat also acts to protect the vital organs from damage, as it forms a layer around the organs to protect from injury. In particular, visceral fat, which is the fat that causes a protruding abdomen called a “beer belly,” is found behind the abdominal wall surrounding the liver, heart, kidneys, intestines, and other organs. Normally, this type of fat functions to protect your vital organs from damage, but when too much visceral fat accumulates, the biologically-active visceral fat cells begin to secrete harmful hormones and other molecules, such as cytokines, that can cause low-level inflammation and increase the risk for heart disease. Because of the proteins and hormones secreted by visceral fat cells that can cause heart disease, type 2 diabetes, high cholesterol, cancer, and stroke, belly fat is often called the most dangerous type of body fat.

But it’s not just visceral fat cells that are biologically active. Fat also serves an important role – this time in a good way – in producing hormones. Body fat, also known as adipose tissue, excretes a large number of hormones called adipokines. Adipokines are in charge of regulating appetite through the hormone leptin, which acts on the brain to control food intake and energy expenditure. Fat is also involved in insulin sensitivity, as insulin, a hormone produced in the pancreas, is responsible for regulating glucose uptake from the bloodstream to use as an energy source by signalling organs to use the energy from glucose as fuel. However, when the body receives more food than it needs, insulin resistance can occur as the body tries to maintain the blood sugar level, but ends up with more insulin being produced and the cells that have already stored as much energy as possible needing more and more insulin to have the same effect. This is the reason why obesity increases the risk for type 2 diabetes as the body’s cells develop resistance to insulin, and ends up needing higher doses of insulin to uptake glucose and metabolize fat.

But besides the involvement with hormones, fats also play an important role in signalling between cells. An important example are myelin sheaths on nerves, which are insulated with lipids around the axons in order to increase the rate of electrical signals by preventing ions from escaping when the action potential travels out of the cell. The formation of the myelin sheath, called myelination, significantly increases the speed that the electrical signals are transmitted, and because of this increased speed from the lipids insulating the axons, these axons are in charge of transmitting signals related to proprioception, which is awareness of the position of the body. 

As a polyunsaturated fat that the body can’t produce, omega-3 and omega-6 essential fatty acids found in fish, flaxseed, and nuts are important in regulating cholesterol, blood clotting, and inflammation. In addition, fats also play an important role in the absorption of vitamins, since the body is unable to effectively absorb vitamin A, D, E, and K without fat, as these vitamins are fat-soluble. This occurs when the vitamins are combined with other lipids and bile acids that are found in the small intestine, that then gets absorbed into the intestinal lining and exported into the lymph. In total, fat is incredibly crucial to your health! There are many essential fatty acids found in nuts, fish, and certain oils that the body is unable to produce naturally that needs to be consumed through food. Fat also has a variety of other functions, including as an efficient energy source for long-term energy, insulating the body as well as insulating neurons, and helping neurons transmit electrical signals. All macromolecules have important functions in the body, including fat, which is why diets that promote cutting out entire food groups are never a good idea. In fact, it was found in a meta-analysis of 70,000 people that the people that ate low-fat diets lost less weight than those who had higher-fat diets. With the structure and function of fat out of the way, let’s explore the complicated history of how fat became associated with weight gain, even though the true culprit may be something else!

“Insulin also has the job of signaling the liver to store excess glucose as glycogen. The liver can only store a certain amount of glycogen at one time, so anything extra then gets converted to fat for longer-term storage, also under the control of insulin.” 

Healthline.com

Check out Part 2 to learn about the history behind our association between fats, sugar, and weight gain, and the corrupt science that shaped our understanding of nutrition for 40 years!

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