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.

Table of Contents

What’s Fat Loss?

Fat loss is a complex physiological process with the goal of reducing total body fat.

Fat loss can be seen from two different perspectives; body composition and health.

Less fat leads to a better physical appearance. When we are on a weight loss, we are aiming for fat loss. We don't only want to lose fat, but also to keep muscle mass

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Fat loss is also an important aspect for health. Fat percentage is a good indicator to predict cardiovascular risk (study).

Lower fat percentage lowers the risk of mortality (study), improves insulin resistance (study), and lower risk of metabolic syndrome (study).

How Is Fat Stored?

During a caloriesurplus, 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 carbohydrates (study). The molecules are transported in the plasma by lipoproteins to end in the adipocyte.

Second, triglycerides can be formed from free 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).

The potential of proteins to become fat is much lower than carbohydrates or fat themselves.

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), to enter the adipocyte.

How is Fat Loss Activated?

Your body is a dynamic structure, and every process is continuously turning 'on' and 'off'.

For this reason, fat loss can't be "activated" at some point and turned off later.

How can we create a favourable environemtn to activate fat loss?

Calorie Deficit

The only and most important requirement for fat loss is to have a calorie deficit prolonged over time (study).

Calories In = Calories Out

To be in a calorie deficit, we need the "Calories In" to be lower than the "Calories Out".

This can be done by 1) lower calorie intake, and 2) higher calorie expenditure.

On a calorie deficit, the remaining energy required to undergo our day a day will be obtained from the adipocytes.

This liberates triglycerides and produce energy from their break down (study)

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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.

How Does Fat Loss Occur?

Fat loss is composed by a series of chemical reactions and physiological processes, with the ultimate goal of using triglycerides from the adipocytes to produce energy.

Fat loss consists of three processes:

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

Lipolysis

Before we can use fat to produce energy, it must be broken down into fatty acids.

This is done in the cytoplasm, forming one glycerol and three fatty acids (study).

Lipolysis is catalyzed by HSL (Hormone-sensitive lipase) (study).

Lipolysis is a highly regulated process.

Insulin acts as inhibitor (study), 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).

Activation and Fat Transport

Fatty acid degradation takes place in the mitochondria (study).

The broken tyriglyceride, now a glycerol backbone and three fatty acids, is converted to acyl CoA to enter the mitochondria.

This happens in a two-step reaction:

Fatty acids are not able to enter the mitochondria. An specialized carnitine carrier system is needed to shuttle acyl CoA and start the beta oxidation (study).

At the end of the process, Acyl CoA enters the mitochondria.

Activation and Fat Transport

Acyl CoA passes through the outer membrane by simple diffusion
CoA is substitutes by carnitine, forming acyl-carnitine in the CPT I
Acyl-carnitine is transported by CAT into the inner mitochondrial matrix
Carnitine is substituted for CoA, forming Acyl-CoA in the CPT II
Carnitine is shuttled back to the intermembrane space for further transport

Beta-Oxidation

Acyl CoA is converted into Acetyl-CoA. This molecule will start the TCA cycle, part of the central metabolism (study).

The final products of the cycle, both acetyl-CoA and NADH/FADH2 are used to produce energy.

Acetyl-CoA will enter the TCA cycle to produce reduced cofactors. These will be driven to the electron transport chain for ATP production.

The NADH and FADH2 produced during beta-oxidation can be directly used for ATP production.

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.

Fat Loss Regulation

Fatty acid oxidation is highly regulated.

As almost all metabolic reactions occuring in our metabolism, regulation is caused by many different factors We've seen how fat loss occurs, but how's it regulated?

Fatis not the preferred substrate to produce energy. Special conditions are needed to start using fats over glucose.

This process is affected by both positive and negative regulation.

Energy status

Energy status determines the degree of fat oxidation.

In normal cases, glucose will always be preferred over fats to be oxidized and produce energy.

A calorie deficit produces a negative energy balance, 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, favours fat oxidation (study).

The ratio NADH/NAD+, also associated to energy status, regulate fat oxidation (study)

Feeback regulation

Concentrations of products and reactants of metabolic reactions affect the reaction, inhibiting or activating it. This is called feedback regulation.

Acyl CoA, an important metabolite of fat oxidation, downregulates the process (study).

High amounts of free fatty acids will inhibit lipolysis (study)

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 your body doesn't need fat to produce energy .

Insulin acts as an inhibitor of fat oxidation, mainly by decreasing triglycerides breakdown (study)

Leptin is a hormone produced by adipocytes to regulate energy balance and hunger. Leptin levels rise when there's no food intake, avoiding starvation. It activates AMPK (study), 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).

Conclusion

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.

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