A New Study Shows Obesity May Be Genetic
Obesity is often attributed to a very simple equation. But evidence is growing that at least a few of the weight gain that plagues modern humans is predetermined.
A new study from the Research Triangle suggests that variants in a gene known as ankyrin-B -- carried by countless Americans -- may cause individuals to put on fat.
Shows that the receptor variation causes cells to suck up glucose. Obesity becomes all but inevitable when diet or an ageing metabolism is added to the equation.
"We call it fault-free obesity," said Vann Bennett, MD, PhD, senior author of this study and George Barth Geller Professor of Biochemistry at Duke University School of Medicine. "We consider this gene might have assisted our ancestors to save energy in times of famine. In present times, where food is plentiful, ankyrin-B variants could be fueling the obesity epidemic."
The results appear that the week of November 13 at the Proceedings of the National Academy of Sciences (PNAS)
The protein ankyrin-B was discovered by Bennett over thirty decades ago. It acts by tethering proteins that are significant into the inside of the membrane of the cell and is present in each tissue. Other researchers and Bennett have connected some diseases and defects in ankyrin-B, including autism, muscular dystrophy, ageing, diabetes and irregular heartbeat.
Several years ago, an MD/PhD pupil working from the Bennett laboratory, Jane Healey, found that mice with cardiac arrhythmia caused by mutations in ankyrin-B were fatter than their litter partners. She generated mouse models that transported two or three common variants of this gene, to find out why.
Damaris Lorenzo, PhD, a postdoctoral fellow in the lab at the time, found that these mice quickly climbed fat, locking away all their calories in fat tissue rather than sending them to burn as energy. These findings were published in 2015 in the Journal of Clinical Analysis.
"The problem is that we still did not how the gene worked," said Bennett. "There's this common belief in the field that much of obesity could be traced back to hunger and the desired control centres that live in mind. But what if it is not all in our mind?"
Lorenzo, currently an assistant professor of cell biology and physiology had her study team knock out the gene at the cells of mice to study that query.
They replicated a number of the experiments that were conducted in the mouse models, which transported mutant versions of ankyrin-B through their bodies. Like previously, the mice gained weight, and also their fat cells doubled despite exercising and eating the same amount. What's more, the weight gain increased as the mice or have been fed a high-fat diet.
"We quickly learned that the higher accumulation of lipids in fat cells "spilt over" to the liver and muscles," Lorenzo said. "The abnormal accumulation of fat in these tissues led to disruption and inflammation of response to insulin, a hallmark of type II diabetes. A similar cascade of events is that which often occurs in people, and that's the reason obesity could be so detrimental to our wellbeing."
After conducting some experiments, Lorenzo revealed that eliminating or mutating ankyrin-B altered the dynamics of Glut4, the protein which enables glucose to enter cells. As a result, the flood gates were opened, allowing sugar to flow into the cells.
Lorenzo wondered whether the mechanism held true. Variants at ankyrin-B are carried by 1.3 percent of Caucasians and 8.4 percent of African Americans, accounting for millions of men and women in the United States alone. Lorenzo discovered that they consumed glucose and saturated fat cells taking these variants. Though it likely has impacts elsewhere in the body, the disease appears to arise in fat tissue.
"We found that mice can become obese without consuming more and that there's an inherent cellular mechanism to describe that weight gain," Bennett said. "This receptor can enable us to recognize at-risk individuals who need to watch what kind of calories that they consume and exercise more to keep their body weight in check."
But Bennett says their findings from the laboratory has to be verified in the overall populace. To accomplish this, the researchers will need to identify individuals and then evaluate traits that are feature, height and weight, and family histories as well as sugar metabolism, to determine the impact of these variations on human wellbeing.
