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How can DNA affect our metabolism?

What is metabolism? Literally defined, metabolism means “to change or alter.” When applied to our anatomy, metabolism describes the way our bodies control the intake, storage, and use of nutrients. This definition is simple enough—but in practice, the process of metabolizing food is anything but. Our body’s metabolism is an intricate system that involves the brain, stomach, heart, pancreas, kidney, brown fat, white fat, beige fat, and many more tissue types. Thanks to decades of effort, scientists have pieced together a detailed understanding of how our metabolism works.

Metabolism is hardwired in our DNA

We feel hungry for a number of reasons, but most simply it’s because our body has detected a lack of readily available nutrients1. We need energy to power our brain, heart, skin, and every other tissue in our body, and we get that energy from food. However, it’s not efficient for us to eat only when we need energy—just as it’s impractical for you to only put gas in your car when you need to drive. Because of this, our body has to be able to extract important nutrients from the food we eat, distribute them to the parts of our body that need them, and then store or discard what’s left.
This, in a nutshell, is the process of food metabolism. If we break it down, you can see that metabolism involves multiple different processes: our body has to recognize when it needs nutrients and then initiate a feeling of hunger, food seeking behavior, food digestion, nutrient distribution, nutrient storing, halting of food seeking behavior, use of stored materials, and disposal of excess materials. It’s a lot to read, much less carry out. But it’s a process that’s hardwired in our DNA2.

A goldfish metabolism

The MC4R gene appears to have been around for a long time. Research into how metabolism differs across animal species have found various versions of the MC4R gene in primates, rats, mice, sheep, cattle, and even goldfish. MC4R appears to contribute to metabolism in some form or another in each species. This suggests that MC4R dates back to a point in time long before humans and goldfish had evolved—all the way back to an ancestor that’s shared between them.3

One of the more well-studied genetic factors linked to metabolism affects a gene known as the melanocortin-4 receptor, or MC4R for short3. Most studies have focused on the way neurons in our brain use this gene and, more specifically, what happens when they can’t use it. Studies in mice and rats have shown that MC4R sits at the intersection of different metabolic processes. For example, when the gene is removed from the mouse genome, researchers observed that mice ate for longer periods of time, ate more food when it was available, used less energy, and were more prone to obesity. These observations suggest that MC4R helps to control the amount of energy we eat and use, and has an overall contribution to the feeling of being hungry. How it does this is not entirely clear, but is an ongoing topic of research3.

In humans, large scale studies have found that some people inherit a rare version of the MC4R gene and these people are found to be overweight slightly less often than those without it3-5. These results, combined with other related measurements, imply that MC4R plays a role in metabolism that’s similar to what has been observed in mice. What’s more, these studies suggest that differences in metabolism and body weight between people may be partially due to variants in their DNA, including variants in MC4R. The full extent of MC4R’s influence on our metabolism is still being investigated3-7, but these early studies make it possible for us to take a personal look at our own metabolism through DNA sequencing.

  1. Amin, Tehmina and Julian G Mercer. “Hunger and Satiety Mechanisms and Their Potential Exploitation in the Regulation of Food Intake” Current obesity reports vol. 5,1 (2016): 106-12.
  2. Kastenmüller, Gabi et al. “Genetics of human metabolism: an update” Human molecular genetics vol. 24,R1 (2015): R93-R101.
  3. Tao, Ya-Xiong. “The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology” Endocrine reviews vol. 31,4 (2010): 506-43.
  4. Heid, Iris M., et al. “Association of the MC4R V103I Polymorphism With the Metabolic Syndrome: The KORA Study.” Obesity, vol. 16, no. 2, 2008, pp. 369–376., doi:10.1038/oby.2007.21.
  5. Geller, Frank et al. “Melanocortin-4 receptor gene variant I103 is negatively associated with obesity” American journal of human genetics vol. 74,3 (2004): 572-81.
  6. Xi, Bo et al. “Association between common polymorphism near the MC4R gene and obesity risk: a systematic review and meta-analysis” PloS one vol. 7,9 (2012): e45731.
  7. Almeida, Sílvia M et al. “Association between LEPR, FTO, MC4R, and PPARG-2 polymorphisms with obesity traits and metabolic phenotypes in school-aged children” Endocrine vol. 60,3 (2018): 466-478.

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