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.

POMEGRANATE DRUG TO AID ALZHEIMERS PARKINSONS DISEASE

Dr Olumayokun Olajide's research will look to produce compound derivatives of punicalagin for a drug that would treat neuro-inflammation and slow down the progression of Alzheimer's disease

The onset of Alzheimer's disease can be slowed and some of its symptoms curbed by a natural compound that is found in pomegranate. Also, the painful inflammation that accompanies illnesses such as rheumatoid arthritis and Parkinson's disease could be reduced, according to the findings of a two-year project headed by University of Huddersfield scientist Dr Olumayokun Olajide, who specialises in the anti-inflammatory properties of natural products.

Now, a new phase of research can explore the development of drugs that will stem the development of dementias such as Alzheimer's, which affects some 800,000 people in the UK, with 163,000 new cases a year being diagnosed. Globally, there are at least 44.4 million dementia sufferers, with the numbers expected to soar.

The key breakthrough by Dr Olajide and his co-researchers is to demonstrate that punicalagin, which is a polyphenol -- a form of chemical compound -- found in pomegranate fruit, can inhibit inflammation in specialised brain cells known as micrologia. This inflammation leads to the destruction of more and more brain cells, making the condition of Alzheimer's sufferers progressively worse.

There is still no cure for the disease, but the punicalagin in pomegranate could prevent it or slow down its development.

Dr Olajide worked with co-researchers -- including four PhD students -- in the University of Huddersfield's Department of Pharmacy and with scientists at the University of Freiburg in Germany. The team used brain cells isolated from rats in order to test their findings. Now the research is published in the latest edition of the journalMolecular Nutrition & Food Research and Dr Olajide will start to disseminate his findings at academic conferences.

He is still working on the amounts of pomegranate that are required, in order to be effective.

"But we do know that regular intake and regular consumption of pomegranate has a lot of health benefits -- including prevention of neuro-inflammation related to dementia," he says, recommending juice products that are 100 per cent pomegranate, meaning that approximately 3.4 per cent will be punicalagin, the compound that slows down the progression of dementia.

Dr Olajide states that most of the anti-oxidant compounds are found in the outer skin of the pomegranate, not in the soft part of the fruit. And he adds that although this has yet to be scientifically evaluated, pomegranate will be useful in any condition for which inflammation -- not just neuro-inflammation -- is a factor, such as rheumatoid arthritis, Parkinson's and cancer.

The research continues and now Dr Olajide is collaborating with his University of Huddersfield colleague, the organic chemist Dr Karl Hemming. They will attempt to produce compound derivatives of punicalagin that could the basis of new, orally administered drugs that would treat neuro-inflammation.

Dr Olajide has been a Senior Lecturer at the University of Huddersfield for four years. His academic career includes a post as a Humboldt Postdoctoral Research Fellow at the Centre for Drug Research at the University of Munich. His PhD was awarded from the University of Ibadan in his native Nigeria, after an investigation of the anti-inflammatory properties of natural products.

He attributes this area of research to his upbringing. "African mothers normally treat sick children with natural substances such as herbs. My mum certainly used a lot of those substances. And then I went on to study pharmacology!"

HUNGER GAMES HOW THE BRAIN BROWNS FAT TO AID WEIGHT LOSS

Researchers at Yale School of Medicine have uncovered a molecular process in the brain known to control eating that transforms white fat into brown fat. This process impacts how much energy we burn and how much weight we can lose. The results are published in the Oct. 9 issue of the journal Cell.

Obesity is a rising global epidemic. Excess fatty tissue is a major risk factor for type 2 diabetes, cardiovascular disease, hypertension, neurological disorders, and cancer. People become overweight and obese when energy intake exceeds energy expenditure, and excess calories are stored in the adipose tissues, which are made up of both white and brown fat. While white fat primarily stores energy as triglycerides, brown fat dissipates chemical energy as heat. The more brown fat you have, the more weight you can lose.

It has previously been shown that energy-storing white fat has the capacity to transform into energy-burning "brown-like" fat. In this new study, researchers from the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, demonstrate that neurons controlling hunger and appetite in the brain control the "browning" of white fat.

Lead author Xiaoyong Yang, associate professor of comparative medicine and physiology at Yale School of Medicine, conducted the study with Tamas Horvath, professor and chair of comparative medicine, and professor of neurobiology and Obstetrics/gynecology at Yale School of Medicine, and their co-authors.

The team stimulated this browning process from the brain in mice and found that it protected the animals from becoming obese on a high-fat diet. The team then studied the molecular changes in hunger-promoting neurons in the hypothalamus and found that the attachment of a unique sugar called "O-GlcNAc" to potassium ion channels acts as a switch to control brain activity to burn fat.

"Our studies reveal white fat "browning" as a highly dynamic physiological process that the brain controls," said Yang. "This work indicates that behavioral modifications promoted by the brain could influence how the amount of food we eat and store in fat is burned."

Yang said hunger and cold exposure are two life-history variables during the development and evolution of mammals. "We observed that food deprivation dominates over cold exposure in neural control of white fat browning. This regulatory system may be evolutionarily important as it can reduce heat production to maintain energy balance when we are hungry. Modulating this brain-to-fat connection represents a potential novel strategy to combat obesity and associated illnesses."