Trait: Fat Metabolism (β-oxidation)

Dr Haran Sivapalan


August 24, 2020

Did you know that fats provide twice as much energy per unit mass compared to carbohydrates and protein?

Accordingly, fats are important both as a fuel source for exercising muscles and as an energy store for times of need (e.g. during fasting).

Through a process called "beta-oxidation," our cells can generate energy by metabolizing one of the building blocks of fats – fatty acids. During exercise and periods of fasting, our bodies break down fat stores to release fatty acids, which can then be used by muscles for fuel.

Your fat metabolism (beta oxidation) trait analyzes how effectively your muscle cells can use fatty acids as a source of fuel. This process is particularly important if you're looking to shed body fat, lose weight and improve your body composition.

How do we get energy from fats?

Breakdown of triglycerides

When we talk about fat in terms of energy, we are typically talking about a specific type of fat molecule called triglycerides. If you’ve ever had your blood fat (or lipid) levels tested in a healthcare setting, one of the results will probably have been for triglycerides (TGs).

Triglycerides are fats composed of two different types of molecule:

  • fatty acids
  • glycerol

It is fatty acids that our cells can use as a fuel source to produce ATP – our cells’ chemical energy currency.

The first stage of getting energy from fat, then, is to break down triglycerides to yield fatty acids.


  • Fats are stored and transported in the body in the form of molecules called triglycerides.
  • Triglycerides are formed of fatty acids and glycerol.
  • Fatty acids can be used by cells to generate energy.

Getting fatty acids from food

Whenever we eat a meal containing fats (triglycerides), our pancreas secretes enzymes, called lipases, into our small intestine. These enzymes break down triglycerides in our food into fatty acids and glycerol, which then cross the intestinal membrane and enter intestinal cells called enterocytes.

Our intestinal cells immediately rebuild the fatty acids and glycerol into triglycerides. The triglycerides are then packaged with another fat-like substance called cholesterol to form fat globules called chylomicrons.

Chylomicrons serve to transport triglycerides in the bloodstream, primarily from the intestine to the liver. Blood vessels supplying our skeletal muscles and adipose (fat) tissue, however, produce an enzyme called lipoprotein lipase. This enzyme breaks down the triglycerides contained within chylomicrons, releasing fatty acids. These fatty acids, called free fatty acids, can then be used by muscle cells for energy, or be converted into fat stores in adipose tissue.

The liver also produces its own triglycerides. These are also packaged with cholesterol into particles called VLDL (very low density lipoproteins), which allows the triglycerides to be transported in the bloodstream.

As with chylomicrons, triglycerides in VLDL are broken down by the lipoprotein lipase enzyme in blood vessels supplying our skeletal muscle and adipose tissue. This process releases fatty acids, which our skeletal muscles can use for energy.


  • Fat from our diet is absorbed in the intestine and packaged into globules called chylomicrons.
  • Chylomicrons contain fat in the form of triglycerides.
  • Chylomicrons circulate and transport triglycerides in our bloodstream.
  • Muscle and fat (adipose) tissue can break down the triglycerides in chylomicrons to release fatty acids.
  • Fatty acids can then be used for energy by muscle or made into fat stores in adipose tissue.

Getting fatty acids from fat (adipose) tissue

In addition to consuming triglycerides from food, we also have plenty of stores of triglycerides in our fat or adipose tissue.

Through a process called lipolysis, fat cells (adipocytes) can break down stored triglycerides, releasing fatty acids into the bloodstream. These fatty acids, termed “free fatty acids”, can then be taken up by muscles and used to fuel muscle contraction.

The breakdown of stored triglycerides into fatty acids (i.e. lipolysis) is stimulated by the hormone adrenaline (epinephrine). As outlined in your Adrenaline Baseline Level trait, adrenaline is your “fight or flight” hormone that is released during exercise and times of stress.

Adrenaline release during exercise, particularly HIIT (High Intensity Interval Training), therefore enhances the breakdown of fat stores and is an effective way of reducing body fat percentage.


  • Our bodies store fat in adipose tissue.
  • Fat cells (adipocytes) store fat in the form of triglycerides.
  • During exercise and fasting, stored triglycerides are broken down into fatty acids.
  • Fatty acids are released into the bloodstream and can be taken up by muscles for energy.

Transport of fatty acids into mitochondria

As you may recall from previous traits, mitochondria are the structures within our cells that are responsible for producing energy. They’re the “powerhouses of the cell” and can use various fuel sources (including fatty acids from the breakdown of fat) to generate energy in the form of ATP.

Before fatty acids can be used for energy, however, they must first enter mitochondria. To enable this, fatty acids are first converted into a molecule called fatty acyl-CoA. One class of enzyme responsible for this reaction is called ACSL (long chain fatty acyl-CoA ligase / synthetase).

The activity of your ACSL enzyme is therefore very important for allowing your mitochondria to use fat (or, more specifically, fatty acids from the breakdown of fat) as a fuel.

Your beta-oxidation (fat metabolism) trait focuses on one particular form of your ACSL enzyme, called ACSL5. This enzyme is encoded by your ACSL5 gene.

Once fatty acids are converted into fatty acyl-CoA, they can then be transported across the mitochondrial membranes to the inner part of mitochondria – called the mitochondrial matrix.

The process of transporting fatty acyl-CoA across the mitochondrial membranes is facilitated by various transport proteins. Some of these transporter proteins (e.g. CPT1 and CTPII) use an amino acid called carnitine. Carnitine is therefore important for allowing your cells to transport and use fats for energy.

Our bodies are capable of making their own supply of carnitine and research suggests that this is enough to meet our daily needs. Nevertheless, some athletes take carnitine as a dietary supplement to boost fat metabolism; although the evidence to support the use of carnitine supplements is mixed.


  • Fatty acids need to enter mitochondria before they can be used for energy.
  • ACSL enzymes convert fatty acids into fatty acyl-CoA, which can then enter mitochondria.
  • Your ACSL5 enzyme allows mitochondria to use fatty acids as a fuel source.

Beta-oxidation of fatty acids to produce energy

Once fatty acids have been converted into fatty acyl-CoA and transported into mitochondria, they can then be used to produce ATP – our cells’ energy currency.

The generation of ATP from fatty acids is called beta oxidation. Through a series of chemical reactions, fatty acyl-CoA is converted into the molecule Acetyl-CoA.

If Acetyl-CoA sounds familiar, it’s because it is also produced when mitochondria use glucose as a fuel. After the first stage of aerobic respiration, Acetyl-CoA is formed from the breakdown of glucose (via pyruvate). Acetyl-CoA then enters the final two stages of respiration – the Kreb’s or Citric Acid cycle and Electron Transport Chain (or Oxidative Phosphorylation) - which generate ATP.

In a similar fashion, Acetyl-CoA formed from the breakdown of fatty acids during beta-oxidation also enters the Kreb’s cycle and Electron Transport Chain. These stages then generate ATP, which can be used to power various cell processes, including muscle contraction.

As the beta-oxidation of fatty acids and aerobic respiration of glucose both provide ATP through shared pathways, fatty acids form a good fuel source when glucose levels are low – for example, when fasting or during prolonged exercise.


  • Beta-oxidation is the process by which cells break down fatty acids to generate energy.
  • In beta-oxidation, fatty acids are converted into Acetyl-CoA.
  • Acetyl-CoA then enters into the last two stages of cell respiration to produce energy in the form of ATP.

Your ACSL5 gene and fat metabolism

Your ACSL5 gene encodes the ACSL5 (long chain fatty acyl-coA synthetase family member 5) enzyme.

As mentioned earlier, this enzyme is responsible for converting fatty acids into fatty acyl-CoA – a crucial step in allowing mitochondria to produce energy from the breakdown of fatty acids.

Research suggests that variants of your ACSL5 gene affect the levels and activity of your ACSL5 enzyme. This, in turn, influences how effectively your cells can use fatty acids for energy.

Furthermore, ACSL5 gene variants have been shown to alter the degree of fat oxidation in response to diet and exercise. On this note, a SNP (single nucleotide polymorphism) of the ACSL5 gene (to which we ascribe the number rs2419621) creates to different gene variants: the ‘T’ allele and the ‘C’ allele.

People carrying the ‘T’ allele are shown to produce higher amounts of the ACSL5 enzyme in their muscles and lose more fat in response to a calorie restricted diet. This may be due to their improved potential to use beta-oxidation of fatty acids to provide energy when glucose levels are low.


  • Variants of your ACSL5 gene affect how well your muscles can break down fatty acids for energy.
  • The ACSL5 gene influences your response to exercise and diet, including weight loss in response to low-calorie diets.

Dr Haran Sivapalan

A qualified doctor having attained full GMC registration in 2013, Haran also holds a first-class degree in Experimental Psychology (MA (Cantab)) from the University of Cambridge and an MSc in the philosophy of cognitive science from the University of Edinburgh. Haran is a keen runner and has successfully completed a sub-3-hour marathon during his time at FitnessGenes.

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