Epigenetics And Obesity: Study Suggests We May Be Able To Alter Genetic Risk Factors
A new study published in the journal Cell may have discovered the reason why obesity genes are triggered in some children born to overweight parents, but not others.
"We're interested in the mechanisms that can make identical twins come out not so identical, and how these mechanisms contribute to disease," said the study’s senior author J. Andrew Pospisilik, a researcher at the Max Planck Institute of Immunobiology and Epigenetics, in a press release. "If twins can come out substantially different from one another, it means that each of us could have come out differently than how we did."
To figure out if the genes associated with obesity risk can be altered, researchers tested twin mice with the same obesity gene mutation. When the gene Trim28 is mutates, it triggers genes to produce either lean or obese individuals. Because the mice shared an identical genetic background, researchers were able to turn genes on and off to see which ones would affect weight gain. This concept is formally known as polyphenism.
"The existence of strikingly different traits among genetically identical organisms has been heavily studied in insects and can explain the existence of castes such as worker and soldier ants or queen bees, for instance," Pospisilik said.
Pospisilk and his team produced large populations of mice twins that did not have the Trim28 gene, but had identical genes and were raised as equally as possible. In time, researchers found the Trim28-deficient mice had strikingly different body masses than those with the Trim28 gene. It turns out the Trim28-deficient mice turned on other genes, such as Nnat and Peg3 —both alter growth and body weight.
Next, researchers examined fat tissue samples from 22 lean and 18 obese pre-pubescent children, and found humans with a Trim28-deficiency were obese like the mice.
"A switch-like mechanism to produce individuals with different traits without changing DNA provides a selective advantage at the population level," Pospisilik said. "Polyphenism allows an emergency or plan B version that gets the species through transient selective pressures."
Genetics aren’t guaranteed prophecies. Your actions and other environmental factors can trigger and influence how genes act within your body, a phenomenon known as epigenetics. Some, for example, believe anorexia is an epigenetic change that occurs within the body despite having the gene for obesity.
"Previously, people would have thought that epigenetics can moderately increase or decrease traits of an organism, and that epigenetic therapies could then alter or combat these shifts," Pospisilik said. “Our study shows that these shifts may not only occur along a continuum, but may also have areas of high stability. This suggests the possibility that we may be able to switch physiology to produce a state that is inherently stable to stay lean or obese."
Source: Pospisilik JA, Dalgaard K, and Landgraf K, et al. Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity. Cell. 2016.