Turning up the internal heat for weight loss- UCP1 genetic variants

The dream for overweight people: 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.

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

  • reduce the consumption of stored energy – OR –
  • increase the amount of energy used

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

Brown Fat and UCP1:

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

There are three kinds of adipose (fat) tissue:

  • White adipose 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; it is usually located around the collar bone and upper back.

Lean adults have been found to have a greater percentage of brown fat than overweight adults. 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 packed fat cells:

So what makes brown fat ‘brown’?  It looks brown under a microscope because it has a lot more mitochondria, which contain iron. These mitochondria contain Uncoupling Protein 1, which is coded for by the UCP1 gene. (UCP1 is also referred to in some studies as ‘thermogenin’.)

Normally, mitochondria produce a little heat as a byproduct of energy production (A/TP 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 A/TP and instead uses it to produce the extra heat.[ref]

UCP1 (Thermogenin) Activation Pathway (Public Domain Image)

UCP1 is found both 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:

Norepinephrine (noradrenaline) signals through a beta-3 adrenergic receptor to activate UCP1 through a series of steps that involved fatty acids.

Activating and Inhibiting UCP1:

So what initiates the norepinephrine signaling? Brown adipose tissue activity is increased through induction of UCP1 by cold temperature and thyroid hormones. Bile acids were also shown to increase thyroid activity through induction of UCP1.[ref]  Other inducers of brown fat include fish oil and iron (only in those that are iron deficient).[ref]

Inhibitors of UCP1 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 would make up for the lack of UCP1 by shivering. 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:

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

The most studied UCP1 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 UCP1 to increased BMI – age and ethnicity may play a role.[ref]  Interestingly, the rs1800592 variant is tied by some researchers to humans adaptation to colder climates.

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

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

There are a couple of other UCP1 variants that have also been linked in a few studies 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: normal risk for obesity

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

  • T/T: normal risk for obesity
  • G/T: slightly increased risk of more abdominal fat
  • G/G: risk of increased abdominal fat[ref]

*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. 



One way to stimulate brown fat is through 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. 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.


Since iron comes into play with UCP1, making sure that you have sufficient iron is important.  But you should always get your iron levels checked before you supplement. 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 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 a powder form as well as in capsules. Good food sources include capers, black olives, buckwheat, and asparagus.


A carotenoid found in brown seaweed called fucoxanthin has also been shown to increase UCP1 activation. 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.


In mice, a diet high in omega-3 fats (specifically DHA) was found to upregulate UCP1 and decrease 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.

More to read:

Related posts:

Growing up ‘big boned’: MC4R gene and obesity

Leptin Receptors: Genetics and Hunger

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2 Comments on “Turning up the internal heat for weight loss- UCP1 genetic variants

  1. Your whole site is so interesting and I love reading every article. I appreciate the effort that goes into all of this!

    • Thanks, Ruby! I do appreciate hearing from people who are getting something out of my website.

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