Utilizing human fats cells, the researchers discovered they might manipulate FTO in cells from people with the obesity-prone model to modify off IRX3 and IRX5, restore thermogenesis to non-risk ranges and change off genes that promote fats storage.
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The researchers came to this conclusion after looking at over 100 tissue and cell types, focusing specifically on the activity of eight genes, which they believed interacted with an FTO.
“Obesity has traditionally been seen as the result of an imbalance between the amount of food we eat and how much we exercise, but this view ignores the contribution of genetics to each individual’s metabolism,” she added.
“Previous studies attempted to uncover a link between FTO and the regulation of appetite or propensity to exercise controlled by the brain”, said the study’s lead and corresponding author Melina Claussnitzer, PhD, an investigator in the Division of Gerontology at BIDMC and Hebrew SeniorLife, visiting professor at MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) and member of the Broad Institute. The discovery could open new pathways for potential prevention and treatment regimes against obesity.
Scientists since long have known that a gene called FTO was related to obesity, but they didn’t know how it actually works.
However, the study findings do not encompass the whole mechanism of obesity, and other genes may be involved.
The net effect is a composition of fat cells that is more amenable to generating energy and heat, and less inclined to sequester into fat stores.
Researchers have discovered a cell circuit that controls whether fat cells burn or store fat is regulated by a master gene that differs among individuals.
The mice didn’t even gain weight on a high-fat diet after scientists used DNA editing technology to switch a signature, from obese to lean, in the genetic region known as “FTO”.
Kellis’s team was able to use gene editing techniques to adjust the functioning of the FTO gene in fat cells, converting fat-storing cells into fat-burning cells – effectively turning white fat beige – and vice versa.
The quest to understand the FTO region was particularly hard because the genetic variants do not affect a protein, Kellis says; rather, they affect a “control region”. “This new pathway controls thermogenesis within the extra plentiful white fats shops as an alternative, and its genetic affiliation with weight problems signifies it impacts global power stability in people”.
Similarly, Dr. Sam Klein, director of the Center for Human Nutrition at Washington University School of Medicine in St. Louis, calls the new paper “a scientific tour de force”. Based on their new findings, obese people have a malfunctioning gene preventing them from burning fat.
About 40 percent of Europeans and 42 percent of Southeast Asians carry the obesity-risk variant, Kellis says. “That tells us that we switched their metabolism from energy storage to energy dissipation”.
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Researchers said they are now forming partnerships with academics and industry to explore therapeutic options – and perhaps a cure – for obesity.
