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They Let Some of Us Eat What We Want, Still Stay Slim
By Jeanie Davis
Sept. 7, 2001 -- They're the people you love to hate; they can eat sugar donuts all day and never gain a pound. Now, a group of Swedish researchers may have an explanation.
Sven Enerbäck, MD, PhD, a medical genetics researcher at Goteborg University in Sweden, and colleagues, have identified a gene called FOXC2 that may partly determine who can pig out without gaining weight -- and who can't.
"The FOXC2 gene could be the natural defense against obesity," says Enerbäck, whose study appears in this week's edition of the journal Cell.
Previous studies, including some involving twins, have pointed to a genetic influence in weight gain. "It's known that if you feed twins 1,000 extra calories per day, some will not increase body weight at all whereas some will convert the extra calories with 100% efficiency to triglycerides -- fat," Enerbäck tells WebMD.
Researchers have pinpointed the FOX family of genes as having a role in regulating this process, he says. But it's been unclear how the genes functioned.
In their study, Enerbäck and colleagues bred mice with high activity levels of FOXC2 in their fat tissue, called adipose tissue.
When the high-FOXC2 mice were fed a high-fat diet, they were less likely to gain weight than comparison mice. In fact, they had 10% body fat compared with the comparison mice, which had 30% body fat on the same diet. The fat cells of the high-FOXC2 mice were also substantially smaller.
Enerbäck's work also has implications for treatment of diabetes, he tells WebMD. The high-FOXC2 mice had lower blood sugar levels after a meal than did the comparison mice, while having the same amount of insulin circulating in their bloodstreams. This meant that they had better insulin sensitivity - a good thing, because it meant they were better able to fend off diabetes.
"Everyone knows someone who can seemingly eat a lot of food without gaining weight," says Enerbäck. "And some of us like myself have to watch very carefully what they eat. While it's possible for obese people to lose weight, it's very, very hard for them to maintain this ideal body weight."
People who can eat a lot without gaining weight may naturally have more active FOXC2, he says.
With the right drug, so could you, he says. "If the drug up-regulates this gene, fewer calories would be converted into triglycerides [and fat] and more would be burned as heat."
In another time, these genes might not have been so helpful. Instead, so-called "thrifty genes" which would preserve energy in fat, helped our forebears survive periods without sufficient food, says Enerbäck. "The genes would also make them more efficient in extracting energy from their surroundings."
However, living in modern times in a calorie-loaded environment, these "thrifty" genes make us prone to developing obesity. "There's a limit at which too-large adipose stores cease to be an advantage and instead become a burden when it comes to survival," he tells WebMD.
While Enerbäck is likely onto something -- as other studies have suggested -- a "word of caution" comes from Luciano Rossetti, MD, co-director of the Diabetes Research Center at Albert Einstein College in the Bronx, N.Y.
"This study deals with brown adipose fat, found mostly in rodents and animals that hibernate," he tells WebMD. "In humans there is very little brown adipose fat. [The study] may or may not be of relevance to human's white fat. Can our white fat be induced to behave more like brown fat? That's what they are trying to imply, but that's completely unproven."
The dramatic changes Enerbäck saw in his mice may not be so dramatic in humans, says Rossetti. "You see threefold differences in weight gain in this study. I'm not sure you'll see that in humans."
Nevertheless, researchers seem to think this is the right direction, he tells WebMD. A category of drugs under development -- called beta-3 adrenergic agonists - is being designed to stimulate the fat cell to do what this FOXC2 factor does.
"This should get us to our dream, to eat like pigs and not gain weight," he says.
By Jeanie Davis
Sept. 7, 2001 -- They're the people you love to hate; they can eat sugar donuts all day and never gain a pound. Now, a group of Swedish researchers may have an explanation.
Sven Enerbäck, MD, PhD, a medical genetics researcher at Goteborg University in Sweden, and colleagues, have identified a gene called FOXC2 that may partly determine who can pig out without gaining weight -- and who can't.
"The FOXC2 gene could be the natural defense against obesity," says Enerbäck, whose study appears in this week's edition of the journal Cell.
Previous studies, including some involving twins, have pointed to a genetic influence in weight gain. "It's known that if you feed twins 1,000 extra calories per day, some will not increase body weight at all whereas some will convert the extra calories with 100% efficiency to triglycerides -- fat," Enerbäck tells WebMD.
Researchers have pinpointed the FOX family of genes as having a role in regulating this process, he says. But it's been unclear how the genes functioned.
In their study, Enerbäck and colleagues bred mice with high activity levels of FOXC2 in their fat tissue, called adipose tissue.
When the high-FOXC2 mice were fed a high-fat diet, they were less likely to gain weight than comparison mice. In fact, they had 10% body fat compared with the comparison mice, which had 30% body fat on the same diet. The fat cells of the high-FOXC2 mice were also substantially smaller.
Enerbäck's work also has implications for treatment of diabetes, he tells WebMD. The high-FOXC2 mice had lower blood sugar levels after a meal than did the comparison mice, while having the same amount of insulin circulating in their bloodstreams. This meant that they had better insulin sensitivity - a good thing, because it meant they were better able to fend off diabetes.
"Everyone knows someone who can seemingly eat a lot of food without gaining weight," says Enerbäck. "And some of us like myself have to watch very carefully what they eat. While it's possible for obese people to lose weight, it's very, very hard for them to maintain this ideal body weight."
People who can eat a lot without gaining weight may naturally have more active FOXC2, he says.
With the right drug, so could you, he says. "If the drug up-regulates this gene, fewer calories would be converted into triglycerides [and fat] and more would be burned as heat."
In another time, these genes might not have been so helpful. Instead, so-called "thrifty genes" which would preserve energy in fat, helped our forebears survive periods without sufficient food, says Enerbäck. "The genes would also make them more efficient in extracting energy from their surroundings."
However, living in modern times in a calorie-loaded environment, these "thrifty" genes make us prone to developing obesity. "There's a limit at which too-large adipose stores cease to be an advantage and instead become a burden when it comes to survival," he tells WebMD.
While Enerbäck is likely onto something -- as other studies have suggested -- a "word of caution" comes from Luciano Rossetti, MD, co-director of the Diabetes Research Center at Albert Einstein College in the Bronx, N.Y.
"This study deals with brown adipose fat, found mostly in rodents and animals that hibernate," he tells WebMD. "In humans there is very little brown adipose fat. [The study] may or may not be of relevance to human's white fat. Can our white fat be induced to behave more like brown fat? That's what they are trying to imply, but that's completely unproven."
The dramatic changes Enerbäck saw in his mice may not be so dramatic in humans, says Rossetti. "You see threefold differences in weight gain in this study. I'm not sure you'll see that in humans."
Nevertheless, researchers seem to think this is the right direction, he tells WebMD. A category of drugs under development -- called beta-3 adrenergic agonists - is being designed to stimulate the fat cell to do what this FOXC2 factor does.
"This should get us to our dream, to eat like pigs and not gain weight," he says.
