Weight Loss While You Relax? Mouse Study Hints It Could Happen Researcher envisions 'game-changer' in obesity treatment

WEDNESDAY, Aug. 19, 2015 (HealthDay News) -- Fat-burning that leads to weight loss while you sleep or relax sounds like a promise from a quack fad diet, but new genetic research into the causes of obesity suggests it might be possible.
Researchers have found a genetic "switch" inside fat cells that can speed up metabolism, prompting the body to burn off excess fat as heat energy even without exercising, according to a report in the Aug. 19 New England Journal of Medicine.

        Laboratory mice lost half their body weight after researchers flipped that genetic switch. And examination of human fat cells has indicated that the process could work much the same in people, said senior author Manolis Kellis, a professor of computer science and computational biology at the Massachusetts Institute of Technology in Cambridge, Mass.
"They were eating the same amount. They were not exercising more," Kellis said of the lab mice. "They were burning energy in the form of heat, both day and night. That tells us that we switched their metabolism from energy storage to energy dissipation."
This newly discovered genetic pathway "would be very targetable with drugs," said Dr. Clifford Rosen, director of clinical and translational research at the Maine Medical Center Research Institute in Scarborough, Maine.
"It is a breakthrough, and so industry is certain to latch onto looking at this much more closely," said Rosen, who wasn't involved in the study. However, any human trials of a fat-burning medication are at least five years away, he added.
Obesity is a global public health challenge, affecting more than 500 million people worldwide and costing at least $200 billion each year in the United States alone, the researchers said in background information with the study. Excess weight contributes to most leading causes of death, including heart disease, stroke, type 2 diabetes and cancer.
"It's just a plague in our society, so being able to reverse obesity can really have societal implications," Kellis said.
Prior research has strongly linked a single gene called FTO to obesity, but up to now scientists have been unable to figure out exactly how mutations in the FTO gene cause people to pack on pounds.
Kellis and his colleagues delved deeper into this by studying the fat tissue of 100 healthy people of European descent. All were of normal weight, but about half carried a mutation that put them at risk for obesity.
The researchers found that the pro-obesity mutation activated two other genes called IRX3 and IRX5, which are inside cells that produce fat tissue.
Most people think of weight control in terms of exercise versus food, Kellis said. If you burn more calories than you eat, then you can expect to lose weight.
But the body also can burn off fat as heat, a process called thermogenesis. This process kicks in when you go out into the cold, for example, burning fat to help keep you warm and functioning, Kellis said.
IRX3 and IRX5 act as master controllers of the thermogenesis process, ordering the body to store excess energy in fat cells rather than burning it off, the researchers found.
By inhibiting these genes, the researchers increased fat-burning in cells from people who have a genetic risk for obesity, the study reported. The reverse also was true: Boosting the IRX3 and IRX5 genes reduced fat-burning in tissue taken from people not genetically prone to obesity.
"Our study provides evidence that manipulation of a specific genetic circuit has significant pro- and anti-obesity effects," said lead investigator Melina Claussnitzer, an instructor in medicine at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston. "This is an important finding that shows in addition to diet and exercise, obesity may result from changes at the cellular level.
"This understanding could pave the way for precision medicine approaches to prevent or reverse obesity in older adults," she added.
Studies in lab mice showed that inhibition of IRX3 caused them to lose weight and increase energy burning without affecting either their levels of physical activity or their appetites, according to findings. They also showed resistance to a high-fat diet.
This discovery is a "big game-changer for obesity" because the genetic switch is located inside a person's fat cells, Kellis added. Up to now, obesity research has largely focused on therapies that would alter the brain to affect appetite and reduce food cravings.
However, people should not assume this advance means an end to exercise or healthy eating, Kellis said. They need to work out and eat right to keep their hearts ticking properly and maintain a host of other positive benefits that come from a healthy lifestyle.
SOURCES: Manolis Kellis, Ph.D., professor of computer science and computational biology, Massachusetts Institute of Technology, Cambridge, Mass.; Clifford Rosen, M.D., director, clinical and translational research, Maine Medical Center Research Institute, Scarborough, Maine; Aug. 19, 2015, New England Journal of Medicine

Oral Contraceptives Have Prevented About 200,000 Cases of Endometrial Cancer in the Last Decade

  NEW YORK --
August 6, 2015 --








Use of oral contraceptives,even for just a few years, gives substantial long-term protection against endometrial cancer, and the longer the pill is used the greater the reduction in risk, according to study published in The Lancet Oncology.

Researchers from the Collaborative Group on Epidemiological Studies on Endometrial Cancer estimate that in the past 50 years (1965-2014) about 400000 cases of endometrial cancer have been prevented by oral contraceptive use in high-income countries, including about 200000 in the last decade (2005-2014).
“The strong protective effect of oral contraceptives against endometrial cancer – which persists for decades after stopping the pill – means that women who use it when they are in their 20s or even younger continue to benefit into their 50s and older, when cancer becomes more common,”* explains study author Professor Valerie Beral, from the University of Oxford in the UK.
She added “Previous research has shown that the pill also protects against ovarian cancer. People used to worry that the pill might cause cancer, but in the long term the pill reduces the risk of getting cancer.
The researchers pooled data on 27276 women with endometrial cancer in 36 studies from North America, Europe, Asia, Australia, and South Africa—virtually all the epidemiological evidence ever collected on the effect of oral contraceptives.
The findings reveal that every 5 years of oral contraceptive use reduces the risk of endometrial cancer by about a quarter (figure 1). In high-income countries, 10 years of oral contraceptive use reduces the risk of developing endometrial cancer before age 75 from 2.3 to 1.3 cases per 100 users (figure 4).
Although oestrogen doses in oral contraceptives have decreased appreciably over the years, with pills in the 1960s typically containing more than double the oestrogen dose of pills in the 1980s, the reduction in endometrial cancer risk was at least as great for women who used the pill during the 1980s as for those who used it in earlier decades. These results suggest that the amount of hormones in the lower-dose pills is still sufficient to reduce the incidence of endometrial cancer, say the authors.
The proportional risk reduction did not vary substantially by women’s reproductive history, adiposity (amount of body fat), alcohol use, tobacco use, or ethnicity.
According to study author Dr Naomi Allen, also from the University of Oxford, UK, “The existing evidence suggests that medium-to-long-term use of oral contraceptives (ie, for 5 years or longer) results in substantially reduced risk of endometrial cancer. Over the past 50 years (1965-2014), we estimate that about 400000 endometrial cancers have been prevented in women before the age of 75 years in high-income countries through the use of oral contraceptives, with about 200,000 prevented during the last decade (2005-14)
                                                                                            SOURCE: The Lancet Oncology