Your Genes and Your Jeans: Making the Connection
As our exploration and comprehension of the human genome continues to evolve, research provides us with the ability to pinpoint specific genes that may increase an individual’s propensity for certain health conditions. While revolutionary and incredibly convenient, this development comes with both good and bad news. Let’s begin with the bad, shall we?
The bad news: Your genes can negatively influence your weight.
One such gene, transmembrane protein 18 (TMEM18), has been implicated in the development of obesity and other metabolic disturbances. This gene is most often found in neurons and is copiously expressed within the hypothalamus and brain stem, both of which are key central nervous system regions in terms of feeding, reward, and gut-brain communication (Sallman Almen et al., 2010). TMEM18 may also be present in other areas of the brain that have been shown to influence food preferences and behaviors, including the amygdala, the hippocampus, and the prefrontal cortex (Rask-Anderson et al., 2012). In a rodent model, the loss of function of TMEM18 ultimately led to a greater body weight, while the over expression of this gene resulted in a decrease in energy intake and an increase in energy expenditure (Larder et al., 2017). Two TMEM18-associated single nucleotide polymorphisms (SNPs), rs6548238 and rs4854344, displayed positive correlations to both waist circumference and body weight and also carried increased risks of obesity in a population of Greek children (Rask-Anderson et al., 2012). A study conducted on Swedish children also investigated rs6548238 as well as rs756131 and found that both SNPs were strongly associated with an increased risk of obesity (Sallman Almen et al., 2010). Lastly, two additional SNPs, rs17042334 (associated with insulin abnormalities) and rs17729501 (associated with obesity), may serve as valuable biomarkers, as they appear to affect the binding and expressive abilities of TMEM18 (Wiemerslage et al., 2016). Ultimately, TMEM18 and its associated SNPs comprise just a piece of the complex puzzle that is energy balance and weight maintenance in the human body. As evidenced above, mutations or alterations in the expression of TMEM18 often have less-than-desirable effects on weight—so where is the positive in all of this?
The good news: Your lifestyle can influence the expression of your genes.
Rejoice! Your genes do not necessarily determine your destiny. In fact, there are several lifestyle interventions that may be helpful in optimizing the function of the TMEM18 gene and its related SNPs.
Exercise: TMEM18 SNP rs4854344 has been strongly linked to increased BMI and body weight in Caucasians; however, when children and adolescents participated in a daily physical activity program, their waist circumference and BMI measurements significantly improved (Zlatohlavek et al., 2018). In other words, the impact of the SNP did not prevent the positive effects of regular exercise from occurring. So—keep moving!
Fasting: In adult flies, TMEM18 expression was drastically reduced—by almost 80 percent—after just 12 hours of starvation; this led to decreased TMEM18 expression in the brain, which may be further implicated in metabolic imbalances and dysfunction (Wiemerslage et al., 2016). Therefore, fasting for an extended period of time may negatively impact TMEM18 and overall metabolism.
Fat Intake: When rats were fed a high-fat diet (60 percent fat) for six weeks, TMEM18 was down regulated in the hypothalamus, liver, and soleus muscle as compared to chow-fed rats (Gutierrez-Aguilar, Kim, Woods, & Seeley, 2012). Thus, a high-fat diet may not be the best option for an individual with alterations in TMEM18, as it may lead to both excessive caloric intake as well as a decrease in the expression of this gene.
Our genes will always play a role in our health. However, the ever-changing realms of epigenetics and nutrigenomics tell us that we have the ability to take our wellbeing into our own hands—and I cannot imagine anything more empowering.
Gutierrez-Aguilar, R., Kim, D.H., Woods, S.C., & Seeley, R.J. (2012). Expression of new loci associated with obesity in diet-induced obese rats: from genetics to physiology. Obesity, 20(2), 306-312.
Larder, R., Sim, M.F.M., Gulati, P., Antrobus, R., Tung, Y.C.L., Rimmington, D.,…Coll, A.P. (2017). Obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation. Proceedings of the National Academy of Sciences of the United States of America, 114(35), 9421-9426.
Rask-Anderson, M., Jacobsson, J.A., Moschonis, G., Chavan, R.A., Sikder, M.A.N., Allzen, E.,…Schioth, H.B. (2012). Association of TMEM18 variants with BMI and waist circumference in children and correlation of mRNA expression in the PFC with body weight in rats. European Journal of Human Genetics, 20(2), 192-197.
Sallman Almen, M., Jacobsson, J.A., Shaik, J.H.A., Olszewski, P.K., Cedernaes, J., Alsio, J.,…Schioth, H.B. (2010). The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children. BMC Medical Genetics, 11, 58.
Wiemerslage, L., Gohel, P.A., Maestri, G., Hilmarsson, T.G., Mickael, M., Fredriksson, R.,…Schioth, H.B. (2016). The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling. Journal of Endocrinology, 229(3), 233-243.
Zlatohlavek, L., Maratka, V., Tumova, E., Ceska, R., Lanska, V., Vrablik, M., & Hubacek, J.A. (2018). Body adiposity changes after lifestyle interventions in children/adolescents and the NYD-SP18 and TMEM18 variants. Medical Science Monitor, 24, 7493-7498.