Mice missing protein burn more fat

PHILADELPHIA — Scientists are learning how they might stoke the body’s fat-burning furnace by turning up a molecular thermostat.

Mice lacking a protein that responds to the hunger-promoting hormone ghrelin burn more energy in their brown fat than other mice, Yuxiang Sun of Baylor College of Medicine in Houston reported December 13 at the American Society for Cell Biology’s annual meeting. This revved-up brown fat helps keep mice lean and energetic into middle age. The finding could eventually lead to a way to help people fight obesity.

Brown fat burns energy instead of just storing it the way white fat does. This metabolically active fat is important in helping rodents and other animals maintain their body temperature. Recently researchers learned that adult humans have brown fat, and that the amount of energy burned by brown fat decreases with age and weight. The discovery has spurred interest in learning how to turn brown fat on.

Sun and her colleagues didn’t start out trying to rev up brown fat. Because the hormone ghrelin has been shown to make animals eat more, the researchers reasoned that blocking the molecule’s activity might reduce appetite and help animals and people lose weight. Sun and her colleagues genetically engineered mice to completely lack either ghrelin or the ghrelin receptor, a protein that interacts with ghrelin and sets off a series of biological reactions in cells that leads to the hormone’s effect.

Disappointingly, mice lacking either molecule ate and exercised just as much as normal mice. But mice lacking the ghrelin receptor burned more energy and stayed lean even as they aged, while normal mice and mice lacking ghrelin tended to gain weight as they got older.

Mice missing ghrelin had a hard time maintaining their body temperature when placed in the cold. But mice without the ghrelin receptor stayed warm. Those pieces of evidence led Sun and her colleagues to examine brown fat in the mutant mice.

Sun’s team found that removing the ghrelin receptor causes brown fat cells to make more of a protein called UCP1. That protein makes the cell’s power plants less efficient and as a result, they release more heat. These inefficient brown fat cells may burn their own supply of fat and then gobble up fat that otherwise would be stored in white fat cells, leading to leaner rodents, Sun speculated.

If researchers can discover why removing the ghrelin receptor turns up brown fat’s furnace, it may be possible to design a drug that will do the same thing. “There may be more than just exercise and willpower that can keep us in shape,” Sun said.

There is no question that increasing the activity of brown fat can have a big effect on weight, said Lewis Landsberg, an endocrinologist at Northwestern University in Evanston, Ill. About 10 percent of a rodent’s total energy expenditure comes from brown fat. Extrapolating to humans, turning up brown fat to burn a similar amount of a person’s calories would be about equal to the energy burned while walking 2.5 miles each day, he said.

Landsberg said that it is not clear whether removing the ghrelin receptor directly affects the energy expenditure of brown fat or if the mutation somehow spurs the sympathetic nervous system to turn up the furnace.

Sun hopes to answer that question by removing the ghrelin receptor in just brown fat cells.

Cells reprogrammed to treat diabetes

PHILADELPHIA — Sperm-forming stem cells in the testes can be converted to insulin-producing cells that could replace diseased ones in the pancreas, researchers from Georgetown University Medical Center in Washington, D.C., reported December 12 at the annual meeting of the American Society for Cell Biology. The new technique is edging closer to producing the amount of insulin needed to cure diabetes in humans.

Ian Gallicano, a developmental biologist at Georgetown, and his colleagues isolated sperm-producing stem cells from the testes of organ donors. These cells could easily revert to an embryonic state, capable of making nearly any cell in the body. The Georgetown researchers treated the cells with chemicals to coax them into mimicking beta-islet cells from the pancreas, the same kind of cells that are compromised in diabetes.

Reprogrammed sperm-producing cells cured diabetes in mice for about a week before their insulin levels dropped again. “If you’re a mouse and you have diabetes, you’re in good shape these days,” Gallicano says.

But cells need to make much more insulin in order to cure diabetes in humans. In islet cells in the human pancreas, insulin accounts for about 10 percent of the proteins secreted by the cell. No stem cell from the testes or anywhere else has come close to making that amount of insulin, Gallicano says. He and his colleagues have developed a new way of programming insulin-producing cells and are getting closer to the goal of creating islet-like cells in which insulin accounts for 1 to 10 percent of the proteins in the cells.
Although testes-derived stem cells would be useful only for men, Gallicano thinks the tricks he’s developing could be adapted to other stem cells that could help women with diabetes too.

Apartments share tobacco smoke

Children in nonsmoking families have higher levels of secondhand exposure if they live in multifamily dwellings.
By Janet Raloff

Children who grow up in apartment buildings are more likely to inhale secondhand tobacco smoke than are kids living in detached homes, a new study finds — even if no one in their household ever lights a cigarette.

“This is the first study to show significant evidence of increased tobacco-smoke exposure among children who live in multi-unit housing,” reports pediatrician Jonathan Winickoff of the Massachusetts General Hospital for Children in Boston, who directed the study. Compared to children who grew up in detached houses, his team finds that those living in apartments excreted 45 percent more cotinine, which is a marker of nicotine exposure. The findings were released online December 13 in Pediatrics.

“Our new study is really the last link in the chain of evidence demonstrating the need for smoke-free buildings,” Winickoff says, “because it proves that children are absorbing that smoke.”

Overall, depending on the type of dwelling in which they lived, cotinine concentrations were quite low, averaging 0.053 to 0.075 nanograms per milliliter of urine among all 5,002 kids, aged 6 to 18. But a host of studies have linked even low-level exposures to behavioral changes and increased risk of allergy and asthma.

“The 2006 surgeon general’s report is clear: There’s really no safe level of secondhand smoke,” notes Gary Adamkiewicz of the Harvard School of Public Health, an environmental health scientist unaffiliated with the new research.

In the new study, Winickoff’s team examined data collected as part of the National Health and Nutrition Examination Survey conducted between 2001 and 2006 by the U.S. Centers for Disease Control and Prevention. Almost three-quarters of children excreted cotinine, including 84.5 percent living in apartments and 70 percent of those from detached homes. There was less than a 1 percent probability that the difference was due to chance. The prevalence of cotinine residues in children from attached homes fell in between.

The common occurrence of the smoke marker among children living in detached houses points to the importance of community exposures, Winickoff says. Kids may have been exposed by being near a parent's smoky clothing, by walking though doorways where smokers are clustered, riding in cars with a smoker or hanging out indoors where smokers previously have lit up.

While dramatic, the new findings hardly come as a surprise, since another recent study measured nicotine from tobacco smoke tainting the air in roughly 90 percent of 49 low-income apartments inhabited by nonsmokers.

“Our study confirmed on-the-ground evidence that folks who live in multi-family housing were reporting,” explains Adamkiewicz, an author of that study. People in nonsmoking residences often could smell smoke, which likely seeped in through ventilation systems, cracks around plumbing or under doors.

Concentrations that his team measured were low — “but not trivial,” he says. They were highest in those households where the residents had reported smelling smoke most frequently. By analyzing air movement in and out of an apartment, “we could calculate how many cigarettes someone would have had to have smoked to yield this level of nicotine in the air,” he says. “And in the apartments of nonsmokers, it started to approach a cigarette a day.” His team reported its findings in the December 2009 Tobacco Control.

The new study takes those results a step further, Winickoff says. “Although we now protect bartenders and people in restaurants in many places from secondhand smoke, we’ve forgotten to protect one critical segment: where children live.” But owing to the strong data that his team has just turned up, he says, “Landlords are soon going to be deciding not whether to go smokefree but how soon to go smokefree.”

And if they don’t, the Department of Housing and Urban Development may force the issue, says toxicologist Bruce Lanphear of Simon Fraser University in Vancouver, British Columbia. “You can’t ban smoking in private housing,” he acknowledges, “but HUD can ban smoking in public housing if there’s sufficient evidence to suggest that it’s in the best interest of kids’ health.”

Another reason the new study is important: It points to housing-related issues, Lanphear says, that at least on a population level may explain why kids in certain ethnic and low-income communities “have higher rates of wheezing or learning problems.”