Obese stomachs tell us diets are doomed to fail

Public release date: 16-Sep-2013 [

Contact: Amanda Page amanda.page@adelaide.edu.au 61-882-225-644 University of Adelaide

The way the stomach detects and tells our brains how full we are becomes damaged in obese people but does not return to normal once they lose weight, according to new research from the University of Adelaide.

Researchers believe this could be a key reason why most people who lose weight on a diet eventually put that weight back on.

In laboratory studies, University of Adelaide PhD student Stephen Kentish investigated the impact of a high-fat diet on the gut’s ability to signal fullness, and whether those changes revert back to normal by losing weight.

The results, published in the International Journal of Obesity, show that the nerves in the stomach that signal fullness to the brain appear to be desensitized after long-term consumption of a high-fat diet.

“The stomach’s nerve response does not return to normal upon return to a normal diet.  This means you would need to eat more food before you felt the same degree of fullness as a healthy individual,” says study leader Associate Professor Amanda Page from the University’s Nerve-Gut Research Laboratory.

“A hormone in the body, leptin, known to regulate food intake, can also change the sensitivity of the nerves in the stomach that signal fullness.  In normal conditions, leptin acts to stop food intake.  However, in the stomach in high-fat diet induced obesity, leptin further desensitizes the nerves that detect fullness.

“These two mechanisms combined mean that obese people need to eat more to feel full, which in turn continues their cycle of obesity.”

Associate Professor Page says the results have “very strong implications for obese people, those trying to lose weight, and those who are trying to maintain their weight loss”.

“Unfortunately, our results show that the nerves in the stomach remain desensitized to fullness after weight loss has been achieved,” she says.

Associate Professor Page says they’re not yet sure whether this effect is permanent or just long-lasting.

“We know that only about 5% of people on diets are able to maintain their weight loss, and that most people who’ve been on a diet put all of that weight back on within two years,” she says.

“More research is needed to determine how long the effect lasts, and whether there is any way – chemical or otherwise – to trick the stomach into resetting itself to normal.”

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This study has been funded by the National Health and Medical Research Council (NHMRC).

Media Contact:

Associate Professor Amanda Page Nerve-Gut Research Laboratory School of Medicine The University of Adelaide Phone: +61 8 8222 5644 amanda.page@adelaide.edu.au

Codeine could increase users’ sensitivity to pain

Contact: Paul Rolan paul.rolan@adelaide.edu.au 61-883-134-102 University of Adelaide

Using large and frequent doses of the pain-killer codeine may actually produce heightened sensitivity to pain, without the same level of relief offered by morphine, according to new research from the University of Adelaide.

Researchers in the Discipline of Pharmacology have conducted what is believed to be the world’s first experimental study comparing the pain relieving and pain worsening effects of both codeine and morphine.

The University’s Professor Paul Rolan, who is also a headache specialist at the Royal Adelaide Hospital, says codeine has been widely used as pain relief for more than 100 years but its effectiveness has not been tested in this way before.

“In the clinical setting, patients have complained that their headaches became worse after using regular codeine, not better,” Professor Rolan says.

“Codeine use is not controlled in the same way as morphine, and as it is the most widely used strong pain reliever medication in the world, we thought it was about time we looked into how effective it really is.”

In laboratory studies, University of Adelaide PhD student Jacinta Johnson found that codeine provided much less pain relief than morphine, but resulted in the same level of increased sensitivity to pain.

“Pain sensitivity is a major issue for users of opioid drugs because the more you take, the more the drug can increase your sensitivity to pain, so you may never quite get the level of relief you need.  In the long term it has the effect of worsening the problem rather than making it better.  We think that this is a particular problem in headache patients, who seem more sensitive to this effect,” Ms Johnson says.

“Both codeine and morphine are opioids but codeine is a kind of ‘Trojan horse’ drug – 10% of it is converted to morphine, which is how it helps to provide pain relief.  However, despite not offering the same level of pain relief, we found that codeine increased pain sensitivity just as much as morphine.”

Professor Rolan says while more research is needed, these laboratory findings suggest a potential problem for anyone suffering from chronic pain who needs ongoing medication.

“People who take codeine every now and then should have nothing to worry about, but heavy and ongoing codeine use could be detrimental for those patients who have chronic pain and headache,” Professor Rolan says.  “This can be a very difficult issue for many people experiencing pain, and it creates difficulties for clinicians who are trying to find strategies to improve people’s pain.”

Ms Johnson presented this research at the 2013 International Headache Congress in Boston, and her work is featured in this month’s issue of Neurology Reviews.

A clinical trial testing a new approach to treating codeine-related headache is now being run by Professor Rolan.

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Media Contact:

Professor Paul Rolan Professor of Clinical Pharmacology The University of Adelaide Phone: +61 8 8313 4102 paul.rolan@adelaide.edu.au

Jacinta Johnson PhD student / Pharmacist School of Medical Sciences The University of Adelaide jacinta.johnson@adelaide.edu.au

Dad’s obesity could be inherited by multiple generations

Contact: Dr. Tod Fullston tod.fullston@adelaide.edu.au 61-883-138-188 University of Adelaide

The sperm of obese fathers could increase the risk of both their children and their grandchildren inheriting obesity, according to new research from  University of Adelaide.

In laboratory studies, researchers from the University’s Robinson Institute have found that molecular signals in the sperm of obese fathers can lead to obesity and diabetes-like symptoms in two generations of offspring, even though the offspring are eating healthily.

The results of the research are published online in The FASEB Journal.

“A father’s diet changes the molecular makeup of the sperm.  With obese fathers, the changes in their sperm – in their microRNA molecules – might program the embryo for obesity or metabolic disease later in life,” says the lead author of the paper, Dr Tod Fullston, who is an NHMRC Peter Doherty Fellow with the University’s Robinson Institute, based in Dr Michelle Lane’s Gamete and Embryo Biology Group.

“For female offspring, there is an increased risk of becoming overweight or obese.  What we’ve also found is that there is an increased chance of both male and female offspring developing metabolic disease similar to type 2 diabetes.

“This is the first report of both male and female offspring inheriting a metabolic disease due to their father’s obesity,” he says.

The study also extended into the second generation of progeny, which showed signs of similar metabolic disorders, including obesity, although it was not as severe as the first generation.

Dr Fullston says even if the obese father does not show any signs of diabetes, metabolic disease similar to diabetes was being seen in two generations of their descendants.

“It’s been known for some time that the health of a mother before, during and after pregnancy can impact on her child’s health, but the father’s health during this period is often overlooked,” Dr Fullston says.

“If our laboratory studies are translatable to humans, this could be a new and as yet unexplored intervention window into the epidemic of childhood obesity.

“A focus on the mother’s health is extremely important, but we’re seeing that the father’s health is also important for conception. It’s possible that by showing additional attention to diet and exercise in the father, this could have a positive impact on his future children and grandchildren.”

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Media Contact:

Dr Tod Fullston NHMRC Peter Doherty Fellow Robinson Institute The University of Adelaide Phone: +61 8 8313 8188 tod.fullston@adelaide.edu.au

Could mistletoe give the kiss of death to cancer?

Contact: Gordon Howarth gordon.howarth@adelaide.edu.au 61-883-137-885 University of Adelaide

      IMAGE:   Health Sciences student Zahra Lotfollahi with a sample of mistletoe extract at the University of Adelaide’s Waite Campus.Click here for more information.

 

Mistletoe has become an important symbol of Christmas but it also has the potential to play a vital role as an alternative therapy for sufferers of colon cancer.

At the University of Adelaide in Australia, scientists are interested in how the extract of mistletoe could either assist chemotherapy or act as an alternative to chemotherapy as a treatment for colon cancer.

Colon cancer is the second greatest cause of cancer death in the Western world.  Mistletoe extract is already authorized for use by sufferers of colon cancer in Europe, but not in some countries such as Australia and the United States due to a lack of scientific testing.

For her Honours research project recently completed at the University of Adelaide, Health Sciences student Zahra Lotfollahi compared the effectiveness of three different types of mistletoe extract and chemotherapy on colon cancer cells.  She also compared the impact of mistletoe extract and chemotherapy on healthy intestinal cells.

In her laboratory studies, she found that one of the mistletoe extracts – from a species known as Fraxini (which grows on ash trees) – was highly effective against colon cancer cells in cell culture and was gentler on healthy intestinal cells compared with chemotherapy.

Significantly, Fraxini extract was found to be more potent against cancer cells than the chemotherapy drug.

“This is an important result because we know that chemotherapy is effective at killing healthy cells as well as cancer cells.  This can result in severe side effects for the patient, such as oral mucositis (ulcers in the mouth) and hair loss,” Ms Lotfollahi says.

      IMAGE:   A sample of the mistletoe extract Fraxini, which has shown the most promise in early laboratory tests at the University of Adelaide.Click here for more information.

 

“Our laboratory studies have shown Fraxini mistletoe extract by itself to be highly effective at reducing the viability of colon cancer cells.  At certain concentrations, Fraxini also increased the potency of chemotherapy against the cancer cells.

“Of the three extracts tested, and compared with chemotherapy, Fraxini was the only one that showed a reduced impact on healthy intestinal cells.  This might mean that Fraxini is a potential candidate for increased toxicity against cancer, while also reducing potential side effects.  However, more laboratory testing is needed to further validate this work,” Ms Lotfollahi says.

“Mistletoe extract has been considered a viable alternative therapy overseas for many years, but it’s important for us to understand the science behind it,” says one of Ms Lotfollahi’s supervisors, the University of Adelaide’s Professor Gordon Howarth, a Cancer Council Senior Research Fellow.

“Although mistletoe grown on the ash tree was the most effective of the three extracts tested, there is a possibility that mistletoe grown on other, as yet untested, trees or plants could be even more effective.

“This is just the first important step in what we hope will lead to further research, and eventually clinical trials, of mistletoe extract in Australia,” Professor Howarth says.

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Zahra Lotfollahi Health Sciences Honours student School of Medical Sciences The University of Adelaide zahra.lotfollahi@student.adelaide.edu.au

Professor Gordon Howarth Cancer Council Senior Research Fellow School of Animal & Veterinary Sciences The University of Adelaide Phone: +61 8 8313 7885 gordon.howarth@adelaide.edu.au