UCP2 Gene: Weight Loss Lifehacks

Turning up the heat on your metabolism is the job of UCP2. The UCP2 gene codes for an uncoupling protein that works in the mitochondria (energy powerhouse) of our cells, producing heat through the uncoupling of the protons.

UCP2 is found in a variety of tissues throughout the body including white and brown fat cells, muscle, liver, kidney, heart, liver, lungs, and more.[ref]

In addition to producing heat from the proton gradient in the mitochondria, UCP2 also mitigates the production of reactive oxygen species (ROS). Thus, it plays a role in energy production, metabolism, and inflammation.

UCP2 genetic variants: 

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Check your genetic data for rs659366 (23andMe v.4, v.5; AncestryDNA):

  • C/C: typical
  • C/T: increased risk of higher BMI, obesity, higher coffee consumption correlated with lower weight
  • T/T: increased risk of higher BMI, obesity T2D, higher coffee consumption correlated with lower weight [ref][ref][ref][ref]

Members: Your genotype for rs659366 is .

Check your genetic data for rs660339 (23andMe v4 only):

  • G/G: typical
  • A/G: higher risk of obesity, increased BMI, waist circumference
  • G/G: higher risk of obesity, increased BMI, waist circumference  [ref] [ref] longer lifespan.[ref]

Members: Your genotype for rs660339 is .


Light: One study in Bali found that the UCP2 genetic variant only contributed to an increased risk of obesity in urban people (compared to rural).[ref] Some environmental differences between urban environments and rural would include the presence of more light at night and a greater likelihood of staying up later, as well as a difference in the types of food eaten.

MelatoninThe reason that I bring up light at night as an urban vs. rural environmental change is the impact of melatonin on UCP2.  Basically, melatonin upregulates UCP2, and it also acts within the cell to reduce excess ROS.[ref]  One way to increase the body’s production of melatonin is to block blue light in the evening with blue-blocking glasses.  This can increase melatonin production by 50% within two weeks.

Cold and Keto: UCP2 is increased by cold and high-fat feeding.[ref]  Ben Greenfield has a good article on cold thermogenesis. One form of high-fat feeding would be a ketogenic diet.

Resveratrol: A high-fat diet, red wine, and resveratrol increase UCP2 expression in muscle tissue (rat study). Grape juice increased UCP2 expression in adipose (fat) tissue.[ref]

Coffee: The research on coffee consumption showed that people with the UCP2 variant had less body fat with more coffee. This was independent of caffeine intake.[ref]

Caution is warranted? Overall, I’m not convinced that trying to increase UCP2 is a good idea to do for the long term. It seems to be a balancing act between reactive oxygen species, inflammation, and energy balance. Plus, UCP2 is upregulated in cancer.[ref]

Related articles and topics:

Growing up ‘big-boned’: MC4R gene and obesity
There are several key players in our body’s regulation of hunger, satiety, and energy expenditure. Two pivotal hormones involved in our desire to eat are leptin and ghrelin. Within that leptin pathway, another key regulator of our body weight is MC4R.

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.


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.