Turning up the internal heat for weight loss: UCP1 gene (2021 update)

The dream of overweight people everywhere: Just turn up the internal heat and naturally burn off the extra fat.

It turns out that genetically some people do have more active ‘internal heat’ and they actually are burning off more energy all the time.

Let’s dive right into how the UCP1 gene turns up internal energy, genetic variants that impair this, and options for revving up the heat.

Brown Fat and UCP1: Burning More Energy

The basis for weight loss, to some degree, hinges on:

  • reduce the consumption of stored energy via reducing appetite  – and –
  • increase the amount of energy used

This is classically thought of as “calories in, calories out”, but it is more complex than research shows. We all know that some people just seem to be able to eat what they want and exercise little while maintaining a lean physique. Genetics at work…

What is brown fat?

Brown fat is one of the factors that come into play for people who are naturally lean.

There are three kinds of adipose (fat) tissue:

  • White adipose (fat) tissue is what we normally think of as fat.
  • Brown adipose tissue, on the other hand, is a highly, thermally-active tissue that is generating a lot of body heat.
  • Beige (or brite) adipose tissue is something in between – perhaps a transition between white and brown.

Babies are born with up to 5% of their body mass as brown fat. This thermally-active fat helps to keep the newborn warm since they are unable to shiver.

Adults have relatively little brown fat. What little brown fat adults do have is usually located around the collar bone and across the upper back.

If comparing lean adults to overweight adults, lean adults have a greater percentage of brown fat.

Mammals that hibernate usually have larger amounts of brown fat to keep them warm in the winter.

There has been a lot of interest in activating brown adipose tissue in order to induce weight loss and to protect against heart disease and diabetic retinopathy. This seems like an ideal weight loss scheme: simply cause the body to increase the amount of heat produced (calories out) by naturally burning fatty acids.

Mitochondria (energy producers) packed into fat cells

So what makes brown fat ‘brown’? It looks brown under a microscope because it has a lot more mitochondria, which contain iron. The UCPI gene codes for Uncoupling Protein 1 found in these mitochondria.  As an example, some studies refer to the UCPI gene as ‘thermogenin’.

Normally, mitochondria produce a little heat as a byproduct of energy production (ATP creation), but the mitochondria in brown adipose tissue that have UCP1 produce quite a bit of heat. Within the mitochondria, UCP1 uncouples the energy generation from ATP and instead uses it to produce the extra heat.[ref]

You can find UCP1 in brown fat and in the retina of the eye. UCP1 is activated by fatty acids and inhibited by purine nucleotides (ADP and GDP).

Let me break that down a little more and add in some details:

UCP1 (Thermogenin) Activation Pathway (Public Domain Image)

Norepinephrine (noradrenaline) signals through a beta-3 adrenergic receptor. 

This receptor then activates UCP1 through a series of steps that involve fatty acids.

Activating and Inhibiting UCP1:

You may be wondering: What initiates the norepinephrine signaling?

Brown adipose tissue activity increases through the induction of UCP1 by cold temperature and thyroid hormones. Also, bile acids can increase thyroid activity through the induction of UCP1.[ref]

Other inducers of brown fat include fish oil and iron (only in those that are iron deficient).[ref]

Inhibitors of the UCP1 gene include beta-blockers. Looking at the pathway description above, beta-blockers block the Beta-3 adrenergic receptors. Iron deficiency also inhibits brown fat activation.[ref]

Mouse studies show that the deletion of the UCP1 gene causes obesity under normal feeding conditions only if the mice are kept in a ‘thermoneutral’ temperature that was the same as their normal body temp.

When mice were kept in what we would consider normal room temperature (18–22°C), they shivered to make up for the lack of UCP1. But when kept at a neutral temperature of 30°C, the mice without UPC1 would get fat on a normal diet with the same number of calories.[ref]

UCP1 Genetic Variants:

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There are several polymorphisms of the UCP1 gene that decrease its activity.

The most studied UCP1 gene variant is -3826A/G (rs1800592) which has been linked in several studies to obesity and diabetic retinopathy risk. A 2013 study found that the variant (C/C genotype*) accelerated an age-related decrease in brown fat activity.[ref]  Another study showed that the variant was only significant in women.[ref]

A 2011 study of young women showed that those with the C allele had less weight loss on a low-calorie diet than those without the polymorphism.[ref] Other studies found that the C/C genotype increases the risk of diabetic retinopathy in those with Type I diabetes.[ref][ref]

Note that not all studies link the UCP1 gene to increased BMI – age and ethnicity may play a role.[ref]  Interestingly, some researchers have tied the  rs1800592 variant to the human adaptation to colder climates.

Check your genetic data for rs1800592 (23andMe v4, v5; AncestryDNA):

  • T/T: typical
  • C/T: probably normal risk for obesity
  • C/C: weak UCP1 activity, higher risk of abdominal fat, obesity; diabetic retinopathy[ref]

Members: Your genotype for rs1800592 is .

There are a couple of other UCP1 gene variants in studies linking to either a higher or lower risk for obesity.

Check your genetic data for rs6536991 (23andMe v4, v5; AncestryDNA):

  • C/C: lower risk for obesity[ref][ref]
  • C/T: lower risk for obesity
  • T/T: typical

Members: Your genotype for rs6536991 is .

Check your genetic data for rs3811787 (23andMe v4 only):

  • T/T: typical
  • G/T: slightly increased risk of more abdominal fat
  • G/G: risk of increased abdominal fat[ref]

Members: Your genotype for rs3811787 is .

*The risk allele is given in the plus orientation to match with 23andMe results. Studies may report it in the minus orientation – so translate as C=G and T=A when reading through the research. 

Lifehacks for activating UPC1, brown fat:

Cold exposure:

One way to stimulate brown fat is by exposing yourself to the cold. This is the most obvious way, and possibly the best way. Things to try:

  • Try a cold shower or just a shower that ends with 30 seconds of cold water.
  • Turn down the heat in the winter (and also save on your energy costs!).
  • There are ice vests made just to induce cold thermogenesis. (Or you could try just putting an ice pack, wrapped in a thin towel, around your neck as a much cheaper option.)

Caveat: Being cold activates brown fat through norepinephrine release from the adrenal glands. Therefore, if you are already stressed out, have poor thyroid function, or have adrenal fatigue, using cold to induce brown fat may be adding stress to your already stressed system. Use your common sense here and don’t stress your body out too much.

Taking cold to more of an extreme: Wim Hof on the benefits of cold therapy

Activating cold receptors without cold exposure:

One way that the body senses cold is through the TRPM8 channel. It is activated when the temperature drops to a certain level.

The TRPM8 channel is also activated by menthol (yep, active component in mint) and ilicin (research chemical). Animal studies with ilicin, which is a more potent activator of TRPM8 than menthol, show that it protects against diet-induced obesity.  The animals are fed a diet that is really fattening (think donuts and pizza), but when exposed to the TRPM8 agonist, they don’t get fat due to increased activation of UPC1 and brown fat.[ref]

Sufficient iron (but not too much):

Since iron comes into play with UCP1, making sure that you have sufficient iron is important.  Before you supplement, always make sure your iron levels are checked. Seriously. (Also check to see if you carry the genetic variants for hemochromatosis– iron overload – before supplementing.)

If you are looking for an inexpensive and easy way to get your ferritin, iron, and TIBC levels checked, UltaLabs has an inexpensive test you can order yourself.

Rutin supplement:

Rutin is a polyphenol found in fruits and vegetables, which stimulates brown fat (animal study).  If you want to supplement with rutin, it is available in powder form as well as in capsules. Good food sources include capers, black olives, buckwheat, and asparagus.

Fucoxanthin supplement:

Fucoxanthin, a carotenoid found in brown seaweed, increases UCP1 activation. For example, a randomized controlled clinical trial in Japan found that carriers of the rs1800592 C/C genotype had a significantly reduced HbA1c level (a marker for insulin resistance) after taking 2mg of fucoxanthin per day for 8 weeks.[ref]  You can buy fucoxanthin as a supplement or eat a lot of seaweed.

DHA in omega-3 fish oil:

In mice, a diet high in omega-3 fats (specifically DHA)  upregulates UCP1 and decreases weight gain. Keep in mind that mice have more brown fat than adult humans have, so this may not give people as big of an effect. Check your genetic data to see if plant omega-3s are a good source for you.

Members: Check out the Weight Loss Topic Report

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Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.