UCP2 Gene: Weight Loss Lifehacks

Turning up the heat on your metabolism is the job for 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. It 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). So it plays a role in energy production, metabolism, and inflammation.

UCP2 genetic variants: 

Check your 23andMe results for rs659366 (v.4, v.5):

  • C/C: Normal
  • C/T: increased risk of higher BMI, obesity
  • T/T: increased risk of higher BMI, obesity T2D[ref] [ref] [ref]

Check your 23andMe results for rs660339 (v4 only):

  • G/G: normal
  • 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]


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]


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]

More to read:




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One Comment on “UCP2 Gene: Weight Loss Lifehacks

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