Posted on 31 March 2022
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In the previous article, we explored the world of lipids – a group of molecules that are essential for our survival. Now it’s time to look at how those lipids are stored throughout the body, with a focus on adipose tissue (fat tissue), the stuff most people think of when we say the word fat. Just as we have seen with lipids, adipose tissue plays an essential role within the body. Why, then, is having a lot of it bad for our health?
Many cell types, especially the muscle and liver cells, have a limited store of lipids in the form of tiny droplets. It’s because of these droplets that wild salmon taste better if caught travelling upstream to mate, as their muscle cells contain more fat than those of ‘spent salmon’ that have already made the journey. In humans, most of the body’s long-term lipid stores lie within the adipose tissue. Adipose tissue can be divided into two main types: white adipose tissue and brown adipose tissue. White adipose tissue is responsible for storing lipids as a reserve of energy. It is made up of white fat cells, or white adipocytes. The space inside each cell is mostly taken up by a single lipid droplet composed primarily of triacylglycerols. The droplets appear white when solid, though in practice adipose tissue is often cream or yellow due to pigments absorbed from the diet.
Lipids are transported into or out of white adipocytes as required, causing the lipid droplet to shrink or expand. When humans gain fat, this is thought to be mainly due to the lipid droplets in their white fat cells growing, while increases in the number of fat cells is thought to be less important during adulthood. Adipocytes store or release lipids into the blood in response to circulating hormones and signals from the sympathetic nervous system – the part of the nervous system involved in the ‘fight or flight’ response. Unfortunately, we have no conscious control over the sympathetic nervous system – otherwise you could quite literally will your fat away!
When adipocytes are instructed to release their stored triacylglycerols, they break them down into their constituent components (glycerol and fatty acids) and release them into the blood. This breakdown process is called lipolysis. Adipocytes are also capable of building new triacylglycerols for storage (lipogenesis), but this process mainly occurs in the liver.
Like white adipose tissue, brown adipose tissue also stores triacylglycerols, but for a very different purpose – the production of heat. Because of this, brown fat is also known as thermogenic (heat-making) adipose tissue. Brown adipose tissue is unique to mammals and its cells store significantly less lipid than white adipocytes. Instead, much of the space within each cell is taken up by mitochondria, the cellular power plants that use nutrients to produce ATP, the cell’s primary fuel. When the brown fat needs to produce heat, brown adipocytes start breaking down their lipid stores and feeding them to the mitochondria. These mitochondria switch to a very inefficient type of ATP production in which most of energy that could be used to produce ATP instead generates heat.
It was once believed that only new-borns and hibernating animals had any brown adipose tissue at all. However, research now suggests that adult humans do still retain some brown adipocytes, though they are rare. Not only that, but some research suggests that chronic exposure to cold conditions may increase the activity and the amount of brown adipose tissue in the body. Since brown adipose tissue consumes calories, it’s not hard to see why this type of fat is perceived as ‘good’ in contrast with the ‘bad’ white adipose tissue. However, there’s nothing intrinsically wrong with white adipose tissue, which fulfils many important roles besides storing lipids.
Storing excess energy is certainly one of white adipose tissue’s most important functions. Without this capability, we would only be able to store a very limited amount of energy, and any excess nutrients would need to be excreted from the body and wasted. This would make us very inefficient organisms and we would be very vulnerable to famine.
However, white adipose tissue isn’t just a storage system – it plays a very active role in regulating how energy is utilised by the body, is involved in controlling appetite, and even has important effects on the immune system. This is because adipocytes don’t just take up and release stored lipids in response to signals from other organs – they also release signals of their own in the form of signalling molecules:
Let’s also not forget that adipose tissue can have a mechanical function depending on where exactly it is located. Subcutaneous adipose tissue (the fat just beneath the skin) contributes to the skin’s thickness and helps retain body heat by acting as an insulating layer. Visceral adipose tissue (the fat surrounding organs) cushions and protects vital organs. Adipose tissue can also act as cushioning in places like the soles of the feet.
If adipose tissue is so great, why can’t we sit back and relax with our morbidly obese BMIs, safe in the knowledge that our organs are well cushioned? Unfortunately, as we are told repeatedly, there is strong relationship between obesity and many fatal chronic conditions, including age-related diseases like heart disease, cancer and neurodegenerative diseases. This relationship exists because in obesity, the systems through which adipose tissue regulates how energy is used and stored start to malfunction.
Signalling between adipose tissue and other tissues is very complex, and scientists are still in the process of studying exactly how it breaks in obesity. A major link between obesity and chronic disease is resistance to the hormone insulin, which is responsible for controlling blood sugar (glucose). When a healthy person eats a meal rich in sugar, the amount of glucose in their blood rises, triggering the release of insulin by the pancreas. Insulin causes cells to absorb more glucose from the blood, bringing blood sugar back down to normal levels within a few hours. However, the cells in obese people don’t respond as strongly to insulin, meaning that they have to produce more insulin than a healthy person to achieve the same reduction in blood sugar. This condition is known as insulin resistance, and is a major risk factor for all age-related diseases.
For a more detailed explanation of why insulin resistance is a huge problem, see this article. In brief, the body stores excess calories as lipids (this includes glucose, which is converted into triacylglycerol by the liver and adipose tissue). When adipose tissue becomes ‘overloaded’ with lipids, the body starts to store more lipids elsewhere, such as in skeletal muscle tissue. We think that when these muscle cells have an abundance of lipids to use as fuel, they refuse to take up glucose in response to insulin, meaning that the liver has to absorb the excess instead. The liver converts that glucose into fatty acids, which build up in liver cells and eventually make them resistant to insulin too.
An insulin resistant liver is disaster for the metabolism, because the liver will now operate as though blood glucose were low (ignoring the signals telling it otherwise) and will start to convert lipids into even more glucose – the opposite of what the body needs. The liver also starts to produce more LDL and less HDL (see part 1), so more cholesterol is carried away from the liver towards other tissues, where it can be deposited in the walls of blood vessels, leading to atherosclerosis. Adipose tissue itself doesn’t escape insulin resistance either. Insulin usually makes adipocytes take up glucose and convert it into lipids (lipogenesis). In insulin resistance, adipocytes refuse to absorb glucose and will instead break down their triacylglycerol and release the products into the blood. This, of course, only makes the situation worse.
Adipose tissue and inflammation
Inflammation is an essential component of the immune system, helping to keep infections at bay until specialised white blood cells (the T and B cells) can mount a more precise response. However, inflammation causes a lot of collateral damage to normal cells, making it problematic if it persists for too long or occurs where it should not. Because of this, inflammation is an important driver of many deadly diseases, including the world’s three most deadly classes of disease: heart disease, cancers, and respiratory diseases. Inflammation is thought to play a fundamental role in the ageing process.
As mentioned earlier, white adipocytes can produce inflammatory signalling molecules, which seems to help them regulate other signals. For example, inflammatory molecules make adipocytes less sensitive to insulin. It has been found that the adipocytes of obese individuals produce significantly more inflammatory molecules than those of non-obese people. These inflammatory molecules may serve as a signal that the adipose tissue is ‘full’ and can’t accept any more lipids. However, in obesity, they not only contribute to insulin resistance, but also enter the circulation and promote continuous, low levels of inflammation in other tissues.
As mentioned previously, adipose tissue produces leptin, which promotes satiety. Since people with more adipose tissue produce more leptin, one might expect those who are overweight or obese to have suppressed appetites, yet in practice the reverse is usually true. This is partly because when levels of leptin remain high for extended periods, the hypothalamus in the brain becomes resistant to its effects. The hypothalamus now operates as though leptin were low, which would normally signal that fat reserves are low. The hypothalamus therefore triggers a hunger response in an erroneous attempt to correct the situation.
While the metabolic effects of being overweight or obese are the most detrimental to one’s health, the psychological and mechanical effects of carrying too much adipose tissue shouldn’t be overlooked. While some people are comfortable with being overweight, many feel unhappy, ugly, and have generally low confidence and self-esteem because of their weight. Those who attempt to lose weight often fail because the metabolic and appetite changes mentioned above make weight loss an uphill battle, which further contributes to low confidence.
Particularly obese individuals may struggle to fit into furniture, vehicles, and may suffer from accidents caused by their weight. Being overweight can cause more skin problems for a variety of reasons, such as the skin being stretched, and the compression of the lymphatic system (part of the immune system) resulting in increased skin infections. Since white adipose tissue insulates the body against heat loss, overweight people may struggle to maintain their body temperature during hot weather and are more at risk of heat stroke.
Hopefully, you now have a clearer picture of how lipids are stored in the body, and how having too much adipose tissue can cause serious health problems. We need adipose tissue to be healthy, and we need lipids in our diet, but not all lipids are equal, nor is all white adipose tissue the same. In part three, it will be time to cover ‘good’ and ‘bad’ fat – what makes one type of lipid more desirable than another, and how does the location in which those lipids are stored affect our health?