BODY CLOCK LINK COULD AID OBESITY TREATMENTS

Scientists at The University of Manchester have discovered that the body clock plays an important role in body fat. Their findings are helping develop new ways of treating obesity and the fatal diseases linked to being overweight.

The researchers, led by Professor David Ray, not only looked at the role of the clock in fat tissue in mice, but also collected samples from patients undergoing weight loss surgery. Fat and blood samples taken both before and after surgery allowed the researchers to compare their biochemistry. The results are published in the journal Diabetes.

Professor Ray explains what they found: "Essentially we discovered that the circadian clock, protein REVERB plays an important role in the safe accumulation of body fat. Usually as fat accumulates there is inflammation in the body which leads to diabetes and heart disease. Our research shows that this process is linked to the body clock."

The team found that REVERB affects obesity-related inflammation by regulating both a hormone that comes from fat, adiponectin, and a master regulator of inflammation A20. Mice lacking REVERB had enhanced fat storage but without the expected inflammation. They also registered higher levels of the hormone adiponectin, suggesting the hormone has an anti-inflammatory role.

Dr David Bechtold was one of the key researchers and says: "Our work demonstrates that it could be possible to switch unhealthy fat to a healthier form by tapping into one of the elements which we discovered. We hope that would mean fewer obese people go on to develop more severe metabolic complications such as type 2 diabetes and heart disease."

As part of the study the researchers took fat and blood samples from morbidly obese patients both before and after weight loss surgery. After the surgery these people had both an increase in the hormone adiponectin in the circulation, but also the inflammation regulator A20 in fat itself. At the same time body fat was healthier, with less of the inflammation linked to diabetes and heart disease.

Professor Ray explains their findings: "Our analysis showed that in morbidly obese people who have undergone weight loss surgery the same pathway from the body clock to inflamed fat is activated. This helps explain why surgery results in rapid health improvements for obese people."

He continues: "We believe our research could open up a novel way to treat obesity without surgery. There is the potential for drug development that could stop so many people dying of obesity related diseases."

A clinical research study is now taking place at The University of Manchester, and Central Manchester University Hospitals NHS Foundation Trust led by Dr Martin Rutter to take this research further. The clinical research study is taking place at the National Institute for Health Research (NIHR)/Wellcome Trust Manchester Clinical Research Facility and The Manchester Diabetes Centre, the first centre to be established in the UK to provide specialist care and education for diabetes patients in the North West.

It is using "clock logic" to treat diabetes. Patients eat, sleep and take medication at times that fit with their body clock in a bid to control the disease. It's hoped the study will demonstrate that strengthening our internal body clock by changing behaviour can be used to treat a condition in a similar way to drugs and surgery.

POTENTIAL LINK BETWEEN ASSISTED REPRODUCTION AUTISM

When prospective parents have trouble conceiving and decide to seek medical help, they typically experience more than a little anxiety and have a host of questions: What are the potential risks to the mother and the baby? What kinds of diseases or other problems are associated with assisted reproduction? And, is one of those problems autism?

As many as one in every 50 children age 6 to 17 is identified as having autism spectrum disorder, which impairs social interaction and communication. The increasing prevalence of autism has boosted the desire to pinpoint causes, and everything from parents' ages to vaccination has come under scrutiny by researchers looking for a link.

Over the past five years, several studies have focused on infertility treatment, partly because of the coincidental rise in both the diagnosis of autism and the use of assisted reproduction, says Sean Ackerman, M.D., a child psychiatry fellow at Fletcher Allen Health Care and clinical instructor in psychiatry at the University of Vermont College of Medicine.

"People are always looking for that silver bullet with autism," he said.

Ackerman and his team found no such link when they studied previously collected DNA data from almost 2,000 children with autism to determine whether assisted reproductive technology -- specifically, in vitro fertilization and two types of intrafallopian transfer -- causes changes in genetic makeup that are associated with autism. The study results are published in the August 2014 Fertility and Sterility.

Until now, no one had studied genetic data, as opposed to epidemiology, to look for a connection between infertility treatment and autism, Ackerman says. He and his team -- including UVM faculty members David Rettew, M.D., associate professor of psychiatry, and Robert Althoff, M.D., assistant professor of psychiatry -- used the reams of data gathered from 2009 to 2011 for the Simons Simplex Collection, a project funded by the Simons Foundation Autism Research Initiative. Ackerman had worked on the project doing medical histories right after completing medical school at the University of Washington.

"When you have a ton of really great data sitting around, it's sort of irresponsible not to use it," he said.

Previous studies looked at the incidence of autism among children conceived with assisted reproductive technology, and results were inconsistent, says Ackerman. Most found no increased risk. A few raised the possibility of a slightly higher risk but also suggested that other factors, including the age of parents using assisted reproduction, could be the reason.

Ackerman developed a fascination with autism before attending medical school, when he took a job as a one-to-one kindergarten aide and was paired with an autistic boy. "I just thought the way he saw the world was so cool," Ackerman says. "It was like going to another country."

Child psychiatry, he decided, was the best specialty to focus on helping children with autism and their parents.

While Ackerman's study doesn't end those parents' quest to determine the cause of the disorder -- which he believes stems from a combination of genetic factors -- it at least removes one of many nagging questions for people approaching infertility treatment.

"Sometimes," he says, "answering a question 'no' is actually comforting."