How does fat loss occur

How Does Fat Loss Occur in our Body? – All You Need to Know

Fat loss is a a concept everyone has heard before. It seems simple, but it is quite more complex than it looks. How does fat loss occur?

In this post we'll give you a brief introduction to fat loss and all the physiological processes taking place when we are trying to lose fat.

With this information you'll be able to assess the effectiveness and uses of the called 'fat burners', and evaluate your diet and progress to get the best results in body composition and health.


Fat loss is a complex physiological process with the ultimate objective of reducing total body fat. It is more specific than weight loss. Here we are referring to specifically body fat, while weight loss simply refers to a drop in weight.

Fat loss can be pursued from two different perspectives; body composition and health. When we talk about body composition, its obvious to think that less fat will lead to a better physical appearance. When we are on a weight loss, we are aiming for fat loss. However, this is not all. We don't only want to lose fat, but also to keep muscle mass (read more HERE)

Fat loss is also an important aspect for health. In fact, fat percentage is better than body mass index at predicting cardiovascular risk (study). Not only that, but lower fat percentage has been associated with lower mortality (study), improves insulin resistance (study), and lower risk of metabolic syndrome (study), among others.

How Is Fat Stored?

When we are in a prolonged calorie surplus, the excess energy is stored in adipocytes in the form of triglycerides (study). These triglycerides stored represent 10-20kg of a healthy male, and slightly more in female (study).

Triglycerides can be synthesized through two main pathways:

First, they can be synthesized in the liver from glycemic substrates (carbohydrates) (study). The synthesized molecules are transported in the plasma by lipoproteins to end in the adipocyte, in where they are shaped and stored.

Second, triglycerides can be formed from free fatty acids by the esterification of a glycerol backbone and three fatty acids (study)

Triglycerides can also be synthesized from amino acids. However, these must be converted to glucose before being further converted to triglycerides (study). Because of the high demands of amino acids in the body, we seldom have excess amino acids to be used for formation of triglycerides. For this reason, the potential of proteins to become fat is much lower than carbohydrates or fat themselves.

Physiology of Fat Storage

Once these molecules are synthesized in the liver, they are transported by lipoproteins, mainly VLDL (very-low density lipoprotein) and LDL (low density lipoprotein) (study). Then, they'll enter the adipocytes, forming droplet-like structures within the adipocyte.

How is Fat Loss Activated?

First of all, we should leave clear that our body is a dynamic structure, and every process is continuously turning 'on' and 'off', depending on the conditions and needs. For this reason, fat loss can't be "activated" at some point and turned off later.

However, we can still favour fat loss by creating a favourable environment to keep it "activated".

Calorie Deficit

As you may have heard before, the only and most important requirement for fat loss is to have a calorie deficit prolonged over time (study).

As we saw in previous posts (read HERE), the model CICO refers to the calorie balance in our organism:

Calories In = Calories Out

To be in a calorie deficit, we need the "Calories In" to be lower than the "Calories Out". Thi can be done by 1) lower calorie intake, and 2) higher calorie expenditure.

When we induce a calorie deficit, the remaining energy required to undergo our day a day will be obtained from the adipocytes, liberating triglycerides and producing energy from their catabolism (study)

Hormone Regulation of Fat Loss

Energy balance seems to be the factor that determines fat loss. But it certainly is not the only one. Fat loss is under a high and strict hormone regulation (study) (study). Ghrelin, insulin, growth hormone, leptin, adrenaline, dopamine,... and the list keeps going.

Keeping all these hormones in range will ensure a correct and potentiated fat loss. On the other side, the under- / overexpression can lead to a disturbed energy metabolism an impared fat loss.

Hormone regulation of Fat Loss


Now we get into matter. Fat loss is composed by a series of chemical reactions and physiological process, with the ultimate goal of excreting the triglycerides from the adipocytes to produce energy.

The processes constituting fat loss are:

  1. Lipolysis: breakdown of triglycerides
  2. Fat transport: transport of fatt acids to the mitochondria
  3. Fat oxidation: energy production from fatty acids


Before we can utilize fat to produce energy, it must be broken down into fatty acids. This is done in the cytoplasm, leading to the formation of one glycerol and three fatty acids (study). Lipolysis is catalyzed by HSL (Hormone-sensitive lipase) (study). As the responsible of catalyzing the breakdown of triglycerides into fatty acids and glycerol, its degree of expression plays an important role in lipolysis.


Lipolysis is a highly regulated process. Insulin, for example, acts as inhibitor (study), thus favouring the use of glucose for energy production. On the other hand, cAMP, a molecule associated with low energy status, acts as an activator (study). This mechanisms allows our body to efficiently produce energy from fats when needed.

Activation and Fat Transport

Mitochondria is where fatty acid degradation takes place (study). But prior to that, the broken tyriglyceride, now a glycerol backbone and three fatty acids, must be converted to acyl CoA to be able to enter the mitochondria. This happens in a two-step reaction, as shown below:

Fatty acid Activation

From the firs reaction, ATP is required. Because the reaction is freely reversible and has a equilibrium of 1, hydrolisis of two pyrophosphates (PPi) from ATP occurs, forming a water molecule and AMP. This ensure the reaction is irreversible under biological conditions.

Because the inner mitochondrial membrane is impermeable to fatty acids, an specialized carnitine carrier system is needed to shuttle acyl CoA and start beta oxidation (study). This is a set of enzymatic reactions and active transprts between acyl CoA and carnitine, leading to the entrance of acyl CoA into the mithocondrial inner matrix:

  1. Acyl CoA passes through the outer membrane by simple diffusion
  2. CoA is substitutes by carnitine, forming acyl-carnitine in the CPT I
  3. Acyl-carnitine is transported by CAT into the inner mitochondrial matrix
  4. Carnitine is substituted for CoA, forming Acyl-CoA in the CPT II
  5. Carnitine is shuttled back to the intermembrane space for further transport
Transport of fatty acids


Now that Acyl CoA is in the mitochondrial matrix, we need to convert it into Acetyl-CoA, molecule starting the TCA cycle, part of the central metabolism (study).

This is a cyclic pathway in where the acyl CoAs are shortened, releasing two acetyl-CoA for each cycle (study). The final products of the cycle, both acetyl-CoA and NADH/FADH2 are used for further energy production.

Acetyl-CoA, on its hand, will enter the TCA cycle to produce reduced cofactors that will be driven to the electron transport chain for ATP production. On the other hand, the NADH and FADH2 produced during beta-oxidation can be directly used for ATP production.

Beta-oxiation of fatty acids

After Beta-Oxidation

Depending on the energy needs, acetyl-CoA may not be needed to its fully extent. In this case, the remaining acetyl-CoA can be converted into acetoacetate (study), the first ketone body in ketogenesis. Acetoacetate, on its hand, can be converted to beta-hydroxybutyrate (BHB), which can freely move between different tissues looking for new opportunities of energy production. In the new tissue, BHB can be converted back to acetoacetate and acetyl-CoA, entering the TCA cycle and producing energy.

Ketogenesis from fatty acids


Fatty acid oxidation is a highly regulated metabolic process. As almost all metabolic reactions occuring in our metabolism, regulation is caused by a multifactorial component. We've seen how fat loss occurs, but how's it regulated?

Because fat is not the preferred substrate for energy production under normal physiological conditions (study), special conditions must be met in order to start oxidizing fats over glucose to produce energy.

This process is affected by both positive and negative regulation. This creates a matrix of possibilities and narrow the conditions at which fat is used for energy production.

Energy status

Energy status determines the degree of fat oxidation. In normal cases in where subjects follow a normal carbohydrate intake, glucose will always be preferred over fats to be oxiized and produce energy. However, calorie deficit produces a negative energy balance from our diet, and the remaining energy is obtained from fats. Therefore, calorie deficit induces lipolysis, fat transport and consequent fat oxidation (study).

The metabolic pathway AMPK, activated during low energy status, acts as an activator of fat oxidation (study). Moreover, the ratio NADH/NAD+, also associated to energy status, regulate fat oxidation (study)

Feeback regulation

Generally, concentrations of products and reactants of metabolic reactions affect the reaction, inhibiting or activating it. This is called feedback regulation. Acyl CoA, a important metabolite of fat oxidation, has shown to downregulate the process (study). Similarly, high amounts of free fatty acids will inhibit lipolysis (study)

Fat Loss regulation

Hormone Regulation

Hormones play an important role regulating fat loss. The main hormone regulators are insulin, leptin, adiponectin and glucagon. 

Insulin is a hormone secreted when glucose is high, transporting and allowing the glucose to enter the cell (study). When insulin is high, it means there's large amounts of glucose, and fat is not needed to produce more energy. Thus, insulin acts as an inhibitor of fat oxidation, mainly by decreasing triglycerides breakdown (study)

Leptin, on its hand, is a hormone produced by adipocytes to regulate energy balance and hunger. Regulating hunger, leptin levels rise when there's no food intake, avoiding starvation. Leptin activates AMPK (study), consequentlya activating fat oxidation.

Adiponectin is a hormone involved in regulating glucose and fat metabolism. It protects agains insulin resistance and atherosclerosis (study). Adiponectin activates AMPK (study), stimulating glucose and fat oxidation. Not only that, but it also activates PPAR-α, key transcription factor of fat oxidation (study)

Glucagon, as the bad brother of insulin, is secreted when glucose levels are low to promote gluconeogenesis and fat oxidation (study).


Fat loss is the physiological process by which the fat in the adipocytes is used for energy production. Buw how fat loss take place?

This process is composed by lipolysis, fat transport and beta-oxidation. All three steps are required if we want to lose fat.

In this post, we've gone through the main steps to understand how fat loss occurs. Late, we focused on regulation of fat loss and different aspects of fat loss regulation.

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