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Buried Genes Could Help Explain Why Humans Are The 'Fat Primate'

MIKE MCRAE
28 JUN 2019

It's no secret that we humans tend to carry a little more padding on our bones compared to our closest living primate relatives. Even without a diet of doughnuts and Netflix, evolution has left us with bodies that hoard fat.

 

An analysis of fat tissues from different primates has found that some of it could come down to subtle differences in how cells package DNA, making it harder for us to convert our spare tyre into the kind of fat that burns easily.

Biologists from Duke University found that unlike chimpanzees and macaques, we humans don't have easy access to sets of calorie-converting genes in our fat cells. As a result, the rich supply of lipids stashed away in our fatty tissue tends to stay put unless we work overtime to burn them away.

This isn't a recent phenomenon imposed by couch potato lifestyles, either. While other primates tend to have less than 9 percent body fat in the wild, healthy humans can easily carry as much as twice this amount.

"We're the fat primates," says Devi Swain-Lenz, a researcher in functional genomics at Duke University.

Such a significant metabolic difference is made all the more curious considering any random sequence of human and chimpanzee DNA differs by just a couple of percent.

To learn how small differences in coding might account for big contrasts in waistline, Swain-Lenz and her team took samples of fat-storing adipose tissue from chimpanzees, humans, and a more distant relative, the rhesus macaque.

 

There are, in fact, two types of fat tissue you need to know about: brown and white. Brown adipose tissue holds its fat in tiny droplets surrounded by energy-converting mitochondria. Its main purpose is to quickly fuel heat generation when temperature drops by powering shivering muscles.

Meanwhile, white fat stubbornly holds onto its reserves, providing not just a back-up fuel supply but acting as a physical layer of protection and thermal insulation. It's this tissue that expands in times of plenty, and the kind of fat the researchers were most interested in.

To better understand what might be happening on a genetic level, the team looked for areas of DNA that were 'open for business'. Long DNA strands are typically coiled up protectively inside cells, wrapped around proteins. Their exposed segments are the easy-access templates that enhance and promote sequences.

These so-called open chromatin regions were significantly different between humans and the other two primates. In fact, just under 3,000 regions had were either easier or harder to access in humans compared to chimpanzees.

Importantly, many of the 780 segments that were less accessible in humans regulated neighbouring genes, a significant number of which were related in some way to lipid metabolism.

 

One of these buried sequences, a transcription factor called nuclear factor 1-A, has been previously implicated in building brown fat tissue.

The protein's gene is pretty much the same in humans and chimps, but the fact it's less exposed in our bundled DNA could help explain key differences in why we tend to build up more white fat than brown.

It does raise some interesting questions as to why humans evolved to bury those fat-converting regions in the millions of years since we part ways from chimpanzees.

Brain size seems like a convenient answer. While ours tripled in size, chimp brains have barely budged. The energy demands on a bigger nervous system are considerable, so it makes sense that our bodies prize additional security in our energy reserves in the shape of ample white fat.

However, just because we've had a rummage through our genes, doesn't mean we'll be able to simply fix our fat distribution.

"Maybe we could figure out a group of genes that we need to turn on or off, but we're still very far from that," says Swain-Lenz.

"I don't think that it's as simple as flipping a switch. If it were, we would have figured this out a long time ago."  

This research was published in Genome Biology and Evolution.