New findings from UNC-Chapel Hill and Duke University contribute additional evidence to a growing body of research showing that obesity has a genetic cause, and is not a sign of a character flaw or a lack of will power.
The study published this week in Proceedings of the National Academy of Sciences found that a common genetic variant caused the fat cells of mice to absorb glucose faster than normal, doubling the size of the fat cells. The same mutations are believed to be carried by millions of people who are unaware that they are genetically predisposed to weight gain.
Duke biochemist Vann Bennett dubbed the concept “fault-free obesity.” The gene is believed to have helped our ancestors store energy during periods of food shortages, but it is prone to accumulate excess fat in modern humans who live in developed societies that know only feast but no famine.
The researchers believe the genetic mutations have the same fattening effect on people as on mice, but confirming the hypothesis will require additional research.
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“At this point all we can tell is that it is possible that these mutations might be also causing obesity in people,” said UNC researcher Damaris Lorenzo, the lead author of the study. “But this needs to be confirmed through epidemiological and clinical studies with humans.”
Many people still associate obesity with laziness, surveys indicate, even though research scientists have known for years that the human obesity epidemic has environmental and genetic causes, with various genes potentially contributing to the problem. When a 1997 New York Times article proclaimed: “Genetic Cause Found for Some Cases of Human Obesity,” the research was taken as long-overdue validation by the National Association to Advance Fat Acceptance.
The UNC-Duke research on mice has significant implications for people, as 1.3 percent whites and 8.4 percent of African-Americans carry variants of the gene that can lead to obesity. The genetic mutation – combined with aging or a high-fat diet – increases the likelihood of unhealthy weight gain.
These people can counteract their genetic propensity for weight gain by exercising and avoiding unhealthy food. Bennett said that as personal genetic sequencing drops in price, more people will be able to use their genetic profile to guide their decisions and choices.
“If someone knew that they had an ankyrin-B variant, they would then know to be particularly careful not only about the amount of calories but the type of calorie,” Bennett said.
The study was written by lead author Lorenzo, a UNC cell biologist who previously worked on the project as a post-graduate researcher at Duke. The affected gene – ankyrin-B – was discovered in the 1980s by Duke biochemist Bennett.
The researchers knew from previous experiments that mice with a defect in the gene were overweight, but they could not identify the precise cause of the weight gain because the gene affects other organs that regulate metabolism.
To pinpoint the cause, Lorenzo removed the ankyrin-B gene in the fat tissue of mice. The mice started gaining weight, suggesting that weight gain is linked to the gene itself, not to related organs. The fat cells started hoarding lipids, rather than sharing the calories with other tissues to be burned off as energy.
The genetic condition in mice ultimately leads to a disruption of insulin, common in type 2 diabetes, following a similar chain of events seen in people.
Specifically, Lorenzo found that eliminating or mutating the gene altered the dynamics of a protein that allows glucose to enter fat cells.
The ankyrin-B gene performs a range of functions. It regulates hormonal secretion, cell migration and organelle transport, and stabilizes proteins at membranes. Defects in the gene have been linked to a range of human conditions, such as autism, muscular dystrophy, diabetes and heart arrhythmia.