New Receptor Finding Leads to Possibilities for Creation of Obesity-Treating Drugs

Anahita Kodali, Medical Sciences, News, Spring 2020

Figure 1: Obesity is defined as having a BMI of 30 or higher. BMI stands for body-mass index – it is a measure of the body’s fat based on a person’s height and weight. As shown in this diagram, there are three levels of obesity. Between a BMI of 30 and 34.9, a person is considered “obese.” Between 35 and 39.9, a person is “severely obese.” At 40 or higher, a person is “morbidly obese.”

Image Source: Wikimedia Commons

There is an obesity epidemic in the United States; nationwide, about 36% of the population is obese1, and the prevalence of obesity in children and adolescents is on the rise, with one out of six children and adolescents aged 2-19 being obese2. These numbers are staggering, especially when compared with obesity rates across the globe. In America, about 71% of men and 62% of women are overweight or obese; worldwide, 38% of men and 37% of women are overweight or obese3. For children, about 29% of American boys and girls are overweight or obese; worldwide, about 14% of boys and girls are overweight or obese.

Obesity has several health risks. It is a risk factor for hypertension and heart disease. It also reduces lung capacity and puts people at risk for respiratory infections, raises the risk of stroke, and causes major bone and joint damage4. People who are obese are ten times more likely to develop type two diabetes, which comes with a whole host of other issues and can exacerbate the issues caused by obesity itself4. Finally, obesity actually raises the risk for developing several types of cancer and is thought to cause over ninety thousand cancer deaths annually4. The negative health effects of obesity, coupled with the sobering statistics showing that obesity is on the rise, show that we need to work towards developing better treatments.

An international research team, led by the University of Southern California, was able to identify the precise structure of a key protein receptor involved in metabolism. They looked at the melanocortin 4 receptor (MC4R), which is found in the brain and controls how much energy is stored as fat5; this allows the receptor to regulate the body’s overall energy balance. Mutations in the gene have been linked to several forms of obesity but is thought to be especially important in severe childhood obesity6. By understanding its precise structure, the researchers were able to understand exactly how the receptor interacts with other molecules.

These findings have important implications for the future of obesity treatment. Currently, there are four drugs that target the MC4R; however, these drugs are not strong enough to treat dietary obesity, which is one of the biggest contributors to obesity6. Thus, it is critical that we work towards developing more effective treatments. Because we now have a clear understanding of the receptor’s structure, we will be able to better understand how it interacts with different drugs. There is also the possibility of developing new drugs and uncovering the shortcomings of drugs currently in use. Hopefully in the coming years, this research will help lower the levels of obesity, not just in the United States, but worldwide as well.

 

Bibliography

[1] Flegal KM, Carroll MD, Kit BK, Ogden CL. (2012). Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA. 307:491-7.

[2] An Epidemic of Obesity: U.S. Obesity Trends. (2016, April 12). Harvard University School of Public Health. Retrieved from https://www.hsph.harvard.edu/nutritionsource/an-epidemic-of-obesity/

[3] Matthews, B. S. E., Gorin, A., Carstensen, M., & Upham, B. (n.d.). American Obesity Rates vs. World Obesity Rates – Everyday Health. Everyday Health. Retrieved from https://www.everydayhealth.com/news/are-we-fat-think

[4] The Impact of Obesity on Your Body and Health: ASMBS. (n.d.). ASMBS. Retrieved from https://asmbs.org/patients/impact-of-obesity

[5] Yu, J., Gimenez, L. E., Hernandez, C. C., Wu, Y., Wein, A. H., Han, G. W., … Stevens, R. C. (2020). Determination of the melanocortin-4 receptor structure identifies Ca2 as a cofactor for ligand binding. Science, DOI: 10.1126/science.aaz8995

[6] University of Southern California. (2020, April 23). An obesity protein discovery may lead to better treatments. ScienceDaily. Retrieved April 24, 2020 from www.sciencedaily.com/releases/2020/04/200423154200.htm

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