Bostonia is published in print three times a year and updated weekly on the web.
White and brown fat are the yin and yang of metabolism. We’re all familiar with white fat, the squishy stuff that bulges around our waists after a few too many doughnuts. But brown fat is more mysterious. It’s the good twin—it burns energy, produces heat, and may hold clues to combating obesity.
A new study led by Kenneth Walsh, director of the School of Medicine’s Whitaker Cardiovascular Institute and a MED professor of medicine, sheds light on the life—and death—of brown fat cells and illustrates the important role that brown fat plays in metabolism.
The study, published in the May Journal of Clinical Investigation, shows that feeding mice a high-fat, high-sugar diet causes their brown fat cells to malfunction, a process that Walsh likens to a “death spiral.” While it’s long been known that humans lose brown fat as they age, the study is the first to describe exactly how brown fat cells “whiten,” effectively becoming more similar to white fat.
“The biggest driver today for cardiovascular disease is obesity and metabolic dysfunction,” says Walsh. “That’s what’s bringing people into the clinic. This study further demonstrates the complex interplay between the cardiovascular and metabolic systems.”
White fat looks white because it’s full of molecules called lipids, which the body uses for long-term energy storage. Brown fat has lipids, too, but it is constantly using them like fuel to stoke a fire. Brown fat looks brown because it is packed with mitochondria, the tiny cellular powerhouses that keep us warm and move our muscles. (White fat, conversely, is not very metabolically active and has fewer mitochondria.) For many years, scientists thought that brown fat existed only in small mammals like mice and in newborn human babies, who need help staying warm.
Then, in 2009, scientists found that adults have brown fat, too—a few pockets in their necks and chests. Since lean people have more brown fat than obese people, the scientists suspected that brown fat might somehow play a role in gaining weight or in keeping it off.
“For years, brown fat was a scientific backwater, because we thought it was only in fuzzy little animals and babies,” Walsh says. “Suddenly it became part of the adult metabolic equation. Now it’s one of the hottest topics in metabolism.”
But big questions remain: does brown fat play a significant role in adult human metabolism? Can white fat become brown? Why do we lose brown fat as we age? How exactly does brown fat whiten, and is there a way to stop it?
In the study, Walsh and his colleagues tried to tackle the last question: what is happening, on a molecular level, when brown fat turns white? To answer the question, they fed normal mice high-fat, high-sugar mouse chow—much like the average American diet—and let them eat as much as they wanted. After eight weeks, remarkable changes were apparent: the mice had gained weight (white fat, unfortunately) and become insulin-resistant—a precursor to diabetes. And their brown fat, no longer able to burn energy efficiently, had become engorged with lipids. In effect, the brown fat had begun to turn white.
“You take a normal lab mouse, give it a fast-food diet full of fat and sugar, and it throws them out of whack,” says Walsh. “It totally confuses their metabolism.”
What happened? By studying tissue and blood samples from the mice at different times after starting the fast-food diet, Walsh and his colleagues teased apart the chain of events that led to the demise of brown fat. First, they discovered, the unhealthy diet led to a high level of toxic fatty acids in the brown fat. This led to the malfunction of a gene called VEGFA (vascular endothelial growth factor A), which helps control the growth of blood vessels in adult tissues. Without a well-functioning VEGFA gene, blood vessels feeding the brown fat shriveled and disappeared, sharply reducing its blood supply. Deprived of blood, and thus oxygen, the mitochondria in the brown fat cells couldn’t burn lipids efficiently, so the fuel began to pile up. The result: brown fat turned white.
“It was a pathological cascade, a death spiral,” Walsh says. “Metabolic dysfunction led to the loss of blood vessels, and blood vessel loss impaired brown fat, leading to more metabolic dysfunction. What was really surprising is that the white fat was minimally affected by blood vessel loss, but the brown fat disintegrated.”
Then came the rescue attempt. Walsh and his colleagues used a virus to insert the gene for VEGFA into the brown fat of obese mice. The infusion of VEGFA didn’t bring the mice back to normal, but it had a restorative effect: the mice’s blood vessels stopped withering, the brown fat perked up and improved its function, and the insulin resistance improved.
It’s too early to say whether this work may eventually lead to new treatments for obesity in humans. But it does shed light on the critical role that the growth and atrophy of blood vessels may play in the maintenance of brown fat, and it demonstrates the rapid tumble toward metabolic dysfunction and obesity once brown fat starts to fail. The new knowledge gives clues for potential targets and treatments.
Sadly, I saw nothing of any studies to show whether a change in diet and exercise would have the same effect. It seems today that the chemical and pharmaceutical companies are only to happy to find profit-making chemical or pharmaceutical solutions to problems caused by them in the first place (how much of our food and products we use on our bodies have ingredients that most of us can’t even pronounce). We are like the experimental rats, and instead of eating foods that have not been infused with chemicals, and exercising, we are only to happy to pay for a “magic pill” solution.
Very interesting read,but unfortunately people are getting away from the basic simple lives we had 2-3 decades ago.Things have become very commercial. Big players are marketing junk food, which people walking into the supermarket find it easy to pick up and consume. From there on the weightless institutes take over: diet therapists,liposuction,weight loss massagers,teas,capsules.No one is there to guide you what the right food is.
It calls for a total revolution and education from childhood!
Hope someone can do it!
Seems to me the brown fat in our leaner prehistoric bodies is giving us the available energy to hunt and gather, but once we have enough body fat to get us through the winter, the brown fat shuts down so we can slowly burn the white fat until spring. A good scenario 10,000 years ago; not so good today.
Kudos on this research!! Nutrition education needs to begin in the early years to eat healthy and avoid as well as reverse the obesity epidemic in this country. I took off 40 lbs last year and have kept it off because I do not want to become a diabetes, heart disease, and cancer victim if I can avoid it. Sodas and other sugar items need to be banned in the schools and come off the shelves in the supermarket. If we don’t buy it though then there won’t be the demand and companies won’t have the market and need to sell it. Fifty-plus years ago we did not have all these choices-it was farm to market and we were healthier. Now you wonder why the increase in heart disease and cancer. You are onto something!!
Nutrition needs to become front-page news. It will be a start in reducing health care costs.
Very interesting—Finding being published in medical journals?
Good report! I learned much. However, it seems to me that 50% of us are already obese.