A gene whose mutated form is associated with cancer in humans turns out to have a role in burning calories over a long evolutionary history.
Do you have skinny genes? And I’m not talking about the pants you wore in college but can’t fit into anymore. No, skinny g-e-n-e-s genes are factors found in folks who are naturally svelte. And researchers have just identified one that appears to tell the body’s adipose tissue to burn more fat.
“We all know these people who can eat whatever they want but never gain any weight.”
Josef Penninger is a geneticist at the University of British Columbia. He says that individuals who are effortlessly trim may hold the key to understanding obesity. See, scientists interested in learning how we control our weight have traditionally focused on the things that make you fat, like diet or metabolism ...
“But not really studied why people actually stay skinny. So we thought we’d just turn around the fields and study genetics of thinness.”
Penninger and his colleagues started out by searching a database maintained by a genome center in Estonia for its most slender registrants. And they weeded out people who were listed as having anorexia or other conditions that alter body fat. Then they looked for genetic markers that track with these Skinny Petes.
One gene, in particular, caught their eye: ALK, or the gene for anaplastic lymphoma kinase, is a stretch of DNA whose mutant form has been associated with human cancers.
“But its normal normal function had never been established.”
So the scientists made mutant fruit flies and mutant mice ...
“To really show that the gene associated with thinness in humans makes also flies and mice skinny. And that’s exactly what we found.”
But the mutant gene doesn’t cause the animals to eat less.
“We found that ALK acts in our brains and what it does: it allows our body to burn more calories per same food we eat.”
So the brain tells fat cells to burn more of the fat they have socked away.
“People, mice and, we believe, also flies stay skinny. So this mechanism is evolutionarily conserved from insects to humans and, we believe, opens up an entirely new field of thinness.”
The study is in the journal Cell. [Michael Orthofer et al., Identification of ALK in thinness]
There are already drugs that inhibit the cancer-causing form of ALK, which means that ALK is what scientists call a druggable target.
“So maybe one day we can indeed develop a pill which keeps us thin.”
[The above text is a transcript of this podcast.]