Genes Linked to Age-Related Obesity And Diabetes

Posted on 18 July 2015

In the developed world many people pile on the pounds a little with age but new data suggests certain mutations may make individuals more vulnerable to obesity and related issues as they get older. 

Researchers have found 2 mutations, one severe and one mild (R1788W and L1622I), occurring on a gene for Ankyrin B, which acts as a protein anchor on the cell membrane and mutations have been linked with a range of diseases. The milder, L mutation is present in about 7% of the African American population and could partially explain why diabetes is a particularly pressing problem for this demographic. Although these are not disastrous, as for most of history a lack of food prevented widespread obesity, they appear to make individuals particularly vulnerable to weight gain and associated problems when consuming a more typical ‘modern’ diet. 

“This is one of the first examples of a susceptibility gene that would only be manifested through a modern lifestyle,” said Vann Bennett, M.D., Ph.D., senior author of the study and George Barth Geller Professor of Biochemistry, Cell Biology, and Neurobiology at Duke University School of Medicine. “The obesity epidemic really took off in the 1980’s, when sugary sodas and French fries became popular. It’s not like we suddenly changed genetically in 1980, but rather we have carried susceptibility genes that were exacerbated by this new diet. We think our findings are just the beginning, and that there are going to be many genes like this.”

The R1788W ankyrin-B mutation causes enlarged fat droplets to form. Credit: Damaris Lorenzo

The R1788W ankyrin-B mutation causes enlarged fat droplets to form. Credit: Damaris Lorenzo

When researchers studied these mutations, they appeared to make cells take up glucose faster than normal. Glucose normally enters cells through a transporter called GLUT4 which is ‘activated’ by insulin levels. In mice with the mutations, cells had plenty of GLUT4 transporters unusually working without insulin, allowing greater consumption of glucose. 

‘After conducting a number of biochemistry experiments, Lorenzo discovered that the mice had lots of GLUT4 on the surface of their muscle and fat cells even when there wasn’t any insulin around. That meant that glucose could flow in without necessarily having to bother with the doorbell. This open door policy was an advantage when they were young, because it protected the animals from low insulin levels. But when the mice got older—or switched to a particularly high-fat diet—it made the mice fatter and, eventually, led them to become insulin resistant’

Knowing these mutations which make obesity and therefore diabetes more of a risk could enable people to make clearer lifestyle choices, taking into account their genes and preventing a decline in health with age. Interestingly, the same genes causing issues today may have been an advantage in the past, allowing individuals to quickly store energy after a meal when food was sparse. Now that food is relatively abundant in the developed world, they have become a hindrance instead. 

Read more at Medical Express 

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