Missing Gene Linked to Extreme Obesity

On February 6, 2010, in Uncategorized, by Andrea

More news from Medscape:

Missing Genes Linked to Extreme Obesity

Jennifer Warner

February 4, 2010 — Missing genes may be behind at least some cases of morbid or extreme obesity, according to a new study.

Researchers found that a small but significant portion of morbidly obese people are missing a section of their DNA that may contribute to their obesity.

The results suggest around seven in every 1,000 morbidly obese people are missing this section of their DNA, which contains about 30 genes. This genetic variation was not found in any people of normal weight.

“Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic,” says researcher Philippe Froguel, of the School of Public Health at Imperial College London, in a news release.

Overall, researchers say about one in 20 cases of morbidly obese people is caused by genetics, including previously identified genetic mutations and these missing genes. But many more genetic mutations linked to obesity are yet to be found.

The researchers hope that identifying genetic variations that cause people to be morbidly obese will lead to the development of genetic tests that can help determine the best treatment.

“If we can identify these individuals through genetic testing, we can then offer them appropriate support and medical interventions, such as the option of weight loss surgery, to improve their long-term health,” says Froguel.

In the study, published in Nature, researchers first identified the missing genes in teenagers and adults who had learning difficulties or delayed development.

The results showed 31 people had nearly identical deletions in one copy of their DNA. All of the adults with this genetic variation had a BMI of over 30, which means they were obese.

People inherit two copies of their DNA, one copy from their mother and one from their father. Sometimes one copy of one or more genes is missing and can affect a person’s development, as shown by this study.

In the second part of the study, researchers examined the genomes or genetic maps of 16,053 European people who were either obese or normal weight. They found 19 more people with the same set of missing genes. All of these individuals were morbidly obese.

The study showed people with the genetic deletion tended to be normal-weight toddlers who became overweight during childhood and morbidly obese as adults.

Researchers did not find the genetic deletion in any normal-weight people. Although they do not know the function of the missing genes, previous studies suggest some of them may be involved with delayed development, autism, and schizophrenia.

SOURCES:

Walters, R. Nature, Feb. 3, 2010, online advance edition.

News release, Imperial College London.

Brain, genetics roles probed in obesity

On January 9, 2010, in Uncategorized, by Andrea

Some skinny people think that fat people are lazy.  That we sit around all day and shovel food into our mouths like gluttonous pigs while we complain about being fat at the same time.  There are even pieces in the media claiming that fat people lie when facing dietary scrutiny.  I’ve been there — I’m sure some of you have, too.

Not all of us sit on our asses all day, eating bon-bons and watching Jerry Springer.  I occasionally mix it up with Oprah, too.

(OK, I’m kidding.  You wouldn’t catch me watching either of them even paid, and I cannot tell you the last time I had a bon-bon.. do they even still make them?  Where does one even buy bon-bons in the grocery store?  I couldn’t tell you.)

So when a fat person tells you “I’m genetically fat” they may, you know, actually mean it.  And given some news from JAMA, hey!  Some scientists are believing it as well.

Scientists Probe Brain’s Role in Obesity

Huan J. Chang, MD, MPH

JAMA. 2010;303(1):19.

Chicago—Genetic and environmental influences on the brain may contribute to obesity, suggests research presented at the Society for Neuroscience’s annual meeting here in October.

The meeting provided a timely forum for bringing together basic and clinical researchers who conduct studies of the causes of overeating and obesity, which largely support the concept of obesity as a biological problem rather than an issue of overindulgence.

Ilia Karatsoreos, PhD, a postdoctoral fellow at Rockefeller University in New York, and colleagues studied the effects of changing the circadian rhythm in mice by artificially creating a 20-hour day (10 hours of light and 10 hours of dark). After 6 to 8 weeks, the mice experiencing these shorter days showed weight gain, changes in body temperature rhythms, and levels of metabolic hormones (including leptin and insulin) when compared with the control group. Behavioral changes, which included increased impulsivity and decreased cognitive flexibility (meaning the mice were less able to adopt new strategies in new situations), occurred in conjunction with neural changes in the prefrontal cortex, an area known to be important for regulating these behavioral traits. The findings may be relevant to humans, given the widespread occurrence of both shift work and jet lag.

Several studies explored the role of epigenetic changes—heritable changes in gene expression that act independently of changes in DNA sequence—in obesity. For instance, Tracy Bale, PhD, associate professor of neuroscience at the University of Pennsylvania, and colleagues showed that pregnant mice not only get fatter and show elevated glucose, leptin, and insulin, when fed a high-fat diet, they also produced pups that were longer, weighed more, and had reduced insulin sensitivity (Dunn GA and Bale TL. Endocrinology. 2009;15[11]:4999-5009). These traits persisted into the next generation, although only females were affected. Further study revealed that these second-generation mice had altered programming of their growth hormone axis, a key gene pathway that controls growth and metabolism. In an interview with JAMA, Bale stated that the changes seen in the second generation of mice have “nothing to do with the diet itself as they have never seen the diet. Thus it has to be inherited by an epigenetic mechanism.”

Similarly, studies by Teresa Reyes, PhD, research assistant professor at the University of Pennsylvania, and colleagues suggest that a high-fat diet in pregnant and lactating mice can affect their pups’ brain development, increasing their vulnerability to becoming obese and to engaging in addictionlike behaviors in adulthood. Such pups exhibited a greater preference for sugar solution and a greater physical response to cocaine than did pups of mothers that were fed a standard diet.

Clinical researchers presented other possible mechanisms for overeating and for the preference of high-sugar and high-fat foods. This research was based on the premise that innate biological factors interact with the environment to predispose individuals to eat.

Kathleen L. Keller, PhD, of the New York Obesity Research Center of Saint Luke’s-Roosevelt Hospital Center and Columbia University College of Physicians and Surgeons, and colleagues followed up on animal studies by French researchers demonstrating that dietary fat may be one of the basic tastes (such as sweet, salty, and bitter) and is associated with expression of the gene encoding CD36, a receptor in the tongue found to play a role in fat detection and preference (Faugerette F et al. J Clin Invest. 2005;115[11]:3177-3184). In their work, Keller and colleagues are the first group to report the relevance of the CD36 gene to humans. They found that those who were heterozygous for the gene were less likely to be able to discriminate fat and tended to dislike low-fat and fat-free foods. In their study, humans who could not discriminate fat ate more high-fat meats, sweets, and spreads.

Dana M. Small, PhD, assistant professor at Yale University, and colleagues identified brain regions where response to ingestion of a milkshake may represent a biomarker of weight-gain susceptibility in humans, and that the response is moderated by the Taq1A A1 polymorphism, which is associated with fewer dopamine receptors. In subjects carrying Taq1A A1, the relative activity (as measured by event-related functional magnetic resonance imaging) of the caudate nucleus, part of the brain’s reward system and an important area for habit learning, predicts an individual’s future weight gain over the next year. The researchers also found that response in the dorsal striatum is inversely related to trait impulsivity.

“This means that overweight people with the A1 allele do not experience less food reward but rather that they may be more prone to impulsive eating,” Small said in an interview with JAMA.