Fat, also known as lipids, is the most feared macronutrient of all by those who would like to lose weight. Indeed, it, of all nutrients, can accumulate in an unsightly, harmful and potentially unlimited manner. Moreover, it is the macronutrient that provides the most calories of all: one gram of fat provides 9kcal, which is twice as much as that provided by one gram of carbohydrates or one gram of protein. From a purely chemical point of view, they consist of symmetrically arranged chains of carbon and hydrogen atoms. Like carbohydrates, fats, irrespective of the amount of calories they provide, have effects, on the one hand, such as to promote weight gain and, on the other, such as to promote weight loss.

The effect of fat on IRS-associated PI-3 kinase

  Insulin resistance is mostly caused by an excessive intake of carbohydrates, but, in some cases, it can also be caused by an excess of fats. In the section on carbohydrates, in fact, we saw that fats are not only deposited in adipocytes, but also in myocytes, the muscle cells. And they do this by taking a particular form: medium-chain triglycerides. These fats, when deposited in large quantities within myocytes, can inhibit an enzyme called IRS-associated PI-3 kinase. This enzyme is responsible for moving GLUT-4 from the inner part of the cell (the cytosol) to the membrane. Now, remember that GLUT-4 are those receptors whose job it is to receive the insulin message. If these receptors remain inside the cell, the latter will no longer be able to communicate with the former. As a consequence, once again, the endocrine pancreas will secrete additional insulin, causing the basal levels of the latter in the blood to remain constantly high. Thus, an excessively high-fat diet can lead to insulin resistance.

The effect of fat on HSL

  Just as carbohydrates, by means of insulin, have an inhibitory effect on the action of HSL, fats also exert an equally favourable effect on weight gain. To begin with, remember that HSL is an enzyme and, more specifically, a hormone-sensitive lipase. Its job is to facilitate and speed up the chemical reactions that lead to the emptying of cells of the fats they contain so that they can be burnt. The effect that a high-fat diet has on HSL is again due to the intramuscular accumulation of medium-chain fatty acids. When the diet is excessively high in fat, we have seen that the muscles stockpile it, storing it in the form of medium-chain triglycerides. Now, an excess of intramuscular medium-chain triglycerides causes the activation of an enzyme known as AMPK. AMPK, in turn, inhibits HSL, resulting in a reduction in lipolytic activity.

The effect of fat on mTOR

  Probably few people are aware that muscular people are less likely to gain (dysfunctional) weight. This is because the more muscle cells there are (or the larger they are), the greater the amount of fat that can be stored within them. And the greater the amount of fat stored within myocytes, the less will be stored in adipocytes. Moreover, the antagonism between myocytes and adipocytes is not only about the amount of fat they can ‘steal’ from each other. Instead, it also concerns glucose (remember that if an adipocyte takes glucose from the blood, this sugar is converted into fat and deposited as such). Now, earlier we talked about AMPK activity. Well, another effect of AMPK generally disliked by athletes is that it inhibits the activity of mTOR (mammalian Target Of Rapamycin) which stimulates the production of new muscle mass. In short:

1. a high-fat diet causes accumulation of medium-chain triglycerides inside muscle cells;
2. Excess intramuscular stores of this particular type of fat cause activation of AMPK;
3. AMPK blocks mTOR, whose job is to mediate the production of new muscle mass;
4. Lacking the prerequisites to be endowed with a discrete muscle mass reduces the antagonism between muscle cells and fat cells;
5. fat cells can more easily take up fat and glucose (to be transformed into fat) from the blood, filling up. Hence, you gain weight.

The influence of fat on metabolism and post-workout recovery process

  In the introduction to the section on fats we saw that these nutrients are made up of chains of carbon and hydrogen. Now, in order to best explain how fats can (negatively) affect the metabolism, a little digression into simple chemistry is required: carbon and hydrogen are atoms, and as such have a nucleus, inside which are positively charged protons and uncharged neutrons. Around the nucleus, then, gravitate electrons, which are negatively charged particles. Now, two atoms can bind together chemically by sharing electrons, which will then gravitate around both. And, since elements, such as carbon and hydrogen, differ in the number of particles they possess, some can establish many bonds (because they have many particles), while others can establish only a few. Hydrogen, in particular, can establish only one bond, while carbon can establish four. In chemistry, the number of bonds that an atom is able to make is called its valence. To say, therefore, that hydrogen has valence 1 and that carbon has valence 4 is like saying that hydrogen, in fact, has the ability to make only one bond, while carbon has the ability to make four. Sometimes, however, an atom, while being able to establish more than one bond, sacrifices, let us say, the possibility of making several in order to establish stronger ones. This is possible because sometimes an atom shares with another not one particle, but two or more particles. When this happens, a double bond is said to have taken place, if the electrons shared are two; triple, if the electrons shared are three, and so on. As the attentive reader will have already realised, once the particles have all been shared, the atom no longer has the capacity to form further bonds. Therefore, the carbon that makes up fats has the ability to bond to two other carbon atoms and two hydrogen atoms, thus forming no double bonds (remember, in fact, that carbon has valence 4), or it can form a double bond with another carbon atom and two simple bonds with two hydrogen atoms. Now, depending on the amount of double bonds formed on the carbon chain of a fat, it is possible to classify these macronutrients into:

1. saturated fatty acids, which do not contain any double bonds;
2. monounsaturated fatty acids, which contain only one double bond;
3. polyunsaturated fatty acids, which contain more than one double bond.

Polyunsaturated fatty acids can themselves be classified according to the position of the first double bond from the last atom of the carbon chain. Particularly relevant here are ω-3 (omega-3) and ω-6 (omega-6), which have their first double bond on the third and sixth carbon atom respectively. Let it be clear that this classification is not merely theoretical. Each of these types of fats has, in fact, its own specific function within the human organism. More specifically, whereas saturated fats have a purely energetic value, unsaturated fats have mostly structural, regulatory and transport functions, except for overconsumption, which can lead to an utilisation of unsaturated fats similar to that of saturated fats. Above we mentioned essential fatty acids and eicosanoids, of which the former are precursors. Well, these are all polyunsaturated fats, as is also polyunsaturated arachidonic acid, synthesised from linoleic acid. More precisely, linoleic acid and arachidonic acid are ω-6, while α-linolenic acid, eicosa-penta-enoic acid and docosa-hexa-enoic acid are ω-3. Now, about saturated fats, since, as mentioned, these mostly have an energy function, they are also the ones most responsible for the increase in fat mass. This, however, is only one of the problems to which excessive consumption of foods rich in saturated fatty acids exposes us. This particular group of fats, in fact, like refined foods containing carbohydrates, has a powerful pro-inflammatory action. In other words, following copious ingestion of foods rich in saturated fatty acids, the body’s cells tend to become inflamed. Now, remember that when a cell is inflamed, it tends to reduce its metabolic activity and, consequently, also tends to burn fewer calories.

AMPK and its fat-burning activity

  We have seen that when eating a diet rich in fats, many of them are deposited, in the form of medium-chain triglycerides, inside muscle cells and that this implies an increase in the activity of the AMPK enzyme. Well, this enzyme has, in fact, not only adverse effects on improving body composition and fitness. Instead, it also has positive ones. In fact, AMPK acts as an activator of β-oxidation within muscle cells (remember that ‘beta-oxidation’ is the ‘scientific name’ for the fat-burning activity of cells). In other words, when AMPK is activated, muscle cells are much more likely to burn fat than they would be if this enzyme were inactive.

AMPK and adipocytes

  AMPK does not only act within myocytes (muscle cells). Instead, it also has an action within fat cells. AMPK has the ability to block the synthesis of new cholesterol and other types of fat within adipocytes. This implies that AMPK not only has the ability to stimulate fat-burning activity within myocytes, but can also hinder the accumulation of new fat mass within fat cells.

AMPK and insulin

  We saw earlier that an excess of fat in the diet results in an accumulation of medium-chain triglycerides within the myocytes and that this accumulation causes inhibition of the IRS-associated enzyme PI-3 kinase, resulting in the development of insulin resistance. On the other hand, fats can also reduce insulin resistance. Indeed, AMPK activated within myocytes following the adoption of a high-fat diet may mediate the entry of glucose into muscle cells, facilitating the task of insulin. Such information may perhaps produce some disorientation, but this should not deter one: as is often the case in nutrition, there are both effects. In some people, it is the one that prevails, while in others, the opposite prevails. In fact, whenever you change something in your diet (as well as in the way you train), either qualitatively or quantitatively, a multiplicity of forces are activated within the body. Some of these forces push in one direction (fattening), while others pull in the opposite direction (slimming).

AMPK and glycogen

  When following a hyperglucidic (i.e. high-carbohydrate) diet, glycogen stores (i.e. glucose reserves stored in muscles and liver) are always quite abundant. Now, AMPK, whose activation, as mentioned, is mediated by fats, has the ability to inhibit the transformation of glucose into glycogen. Excess glucose, therefore, is not deposited, but is immediately burnt by the cells.

AMPK and malonyl-CoA

  We have previously seen that malonyl-CoA has two effects that favour fat accumulation:

1. is the precursor of medium-chain fatty acids, into which it often tends to convert;
2. interferes with the activity of the carnitine-dependent complex, hindering β-oxidation.

Well, the AMPK that the body produces when eating a high-fat diet has, among other effects, the ability to inhibit an enzyme called acetyl-CoA-carboxylase, which catalyses the reaction of transforming acetyl-CoA into malonyl-CoA. In other words, when there is a lot of acetyl-CoA-carboxylase in the cells, this tends to transform acetyl-CoA into malonyl-CoA, which then, in turn, by the mechanism seen in the part on carbohydrates and summarised earlier, causes fattening. By adopting a high-fat diet, the activity of AMPK increases and this implies the inhibition of acetyl-CoA carboxylase, which will therefore no longer transform acetyl-CoA into malonyl-CoA, but will instead transform it into aceto-acetyl-CoA (which, in turn, will be transformed into ketone bodies, which are nourished by many of the body’s cells). Thus, the fattening effect of malonyl-CoA is lost.

Fatty acids in the blood and their influence on adipocytes

  When fat-rich food is consumed, it, like any other food, is first digested within the digestive system and then released into the blood stream. When fats in the bloodstream become significant in number, adipocytes change their activity in an apparently paradoxical way: on their membranes, in fact, there are special receptors known as α-2- adrenergic receptors (read alpha two adrenergic) or, more simply, alpha receptors. Alpha receptors, when activated, signal the cells to take up fats from the blood and store them inside. Well, a significant presence of fats within the bloodstream causes inhibition of alpha receptors, resulting in an impediment to liposynthesis (i.e. addition of new fat mass).