Even fit humans carry more body fat than other primates—chimpanzees, for example. So, it’s clear that our relative chubbiness isn’t all about behavior, even though many of us consume junk foods while struggling with sedentary lifestyles. And we can’t blame our genes, either. Humans and chimpanzees have nearly identical DNA sequences. To get the skinny on human fat, we must take a step back from our genes and see how they’re packaged.
That’s exactly what scientists at Duke University have done. They’ve found that in human evolutionary history, critical shifts occurred in our ancestor’s fat cells, shifts that took place at the epigenetic level, where DNA may be bunched up tightly or hang loosely, like the bellows of an accordion. Some of the bunched-up DNA in our fat cells happens to correspond to genes that turn “bad” calorie-storing fat (white fat) into “good” calorie-burning fat (beige or brown fat).
The bunching up keeps these genes inaccessible, ensuring that we maintain larger fat reserves than our primate cousins. Whereas healthy humans have 14–31% body fat, other primates have less than 9%.
To study how fat-transforming DNA is packaged, the Duke scientists, led by biologist Gregory A. Wray, PhD, used a technique called ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) to scan the genomes of humans, chimpanzees, and rhesus macaques. The scientists identified roughly 780 DNA regions that were accessible in chimps and macaques, but had become more bunched up in humans. Examining these regions in detail, the team also noticed a recurring snippet of DNA that helps convert fat from one cell type to another.
Additional details appeared June 24 in the journal Genome Biology and Evolution, in an article titled, “Comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates.” The article indicates that the Duke team paid particular attention to a well-known source of phenotypic divergence, differences in chromatin accessibility in cis-regulatory regions, that is relevant to many traits, including the accumulation of body fat.
“We examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using rhesus macaque as an outgroup,” the article’s authors wrote. “We find that many regions that have decreased accessibility in humans are enriched for promoter and enhancer sequences, are depleted for signatures of negative selection, are located near genes involved with lipid metabolism, and contain a short sequence motif involved in the beigeing of fat.”
The bunching up of many putative regulatory regions associated with the beigeing of fat suggests a mechanism that increases body fat in humans.
“We’ve lost some of the ability to shunt fat cells toward beige or brown fat, and we’re stuck down the white fat pathway,” said Devjanee Swain-Lenz, a postdoctoral associate in biology at Duke and the first author of the current study. It’s still possible to activate the body’s limited brown fat by doing things like exposing people to cold temperatures, she explained, “but we need to work for it.”
Humans, like chimps, need fat to cushion vital organs, insulate us from the cold, and buffer us from starvation. But early humans may have needed to plump up for another reason, the researchers pointed out—as an additional source of energy to fuel our growing, hungry brains.
In the six to eight million years since humans and chimps went their separate ways, human brains have roughly tripled in size. Chimpanzee brains haven’t budged.
The human brain uses more energy, pound for pound, than any other tissue. Steering fat cells toward calorie-storing white fat rather than calorie-burning brown fat, the thinking goes, would have given our ancestors a survival advantage.
Swain-Lenz said another question she gets a lot is: “Are you going to make me skinny?”
“I wish,” she said.
Because of brown fat’s calorie-burning abilities, numerous researchers are trying to figure out if boosting our body’s ability to convert white fat to beige or brown fat could make it easier to slim down.
According to Swain-Lenz, the differences she and her colleagues found among primates might one day be used to help patients with obesity—but we’re not there yet.
“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,” Swain-Lenz admitted. “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.”