The protein of growth differentiation factor-15 (GDF15) can be used as a weight loss agent with no obvious side effects.

Losing weight seems to come easiest among the people who least want it.
, tens of thousands of people suffer from anorexia associated with cancer.
Now, researchers from three large pharmaceutical companies have published articles proving that the culprit behind the condition , a protein called growth differentiation factor-15 (GDF15), helped mice and monkeys lose weight without any noticeable side effects.
currently has five FDA-approved weight-loss drugs for long-term weight management.
they can reduce a patient's weight by an average of 5% to 10%.
, "It's very limited," said Kathleen Saunders, an obesity physician at Weir Cornell Medical School in New York who was not involved in the study.
, many of the drugs used to treat obesity do not have the same specific levels as GDF15.
" Samuel Breit, an immunologist and doctor at St. Vincent's Hospital in Sydney, Australia, has discovered for the first time the potential of GDF15 as a weight-loss agent.
he found that levels of the protein increased 10 to 100 times higher than usual during tumor-induced anorexia in mice with prostate tumors and patients with advanced prostate cancer.
Breit also suggested that GDF15 could be influenced by the brain, although he says the protein's target has puzzled scientists to this day.
to find targets, Sebastian Beck J?rgensen, a diabetes and obesity researcher at Noor and Nord in Denmark, and colleagues screened more than 2,700 proteins that "live" in human cell membranes.
in the cell membrane, these proteins receive molecular signals from outside the cell and transmit information in.
of all these potential collaborators, GDF15 binds to a single protein recepposer called GDNF family receptonic alpha-like (GFRAL), whose function was previously unknown.
the team reported the findings in the journal Nature Medicine.
, the researchers searched the entire brain of mice to find out which GFRAL genes were turned on.
surprisingly, it was found in only two areas of the brain: the last area of what is thought to be a "vomit-induced center" and the solitable nucleoclea that "inhabits" neurons that involve a lot of behavior, including those involved in appetite regulation.
is often a problem for drug development, as most receptors are separated by a blood-brain barrier.
blood-brain barrier is a cellular system that blocks drugs, toxins and microorganisms from the brain.
, however, because the two areas containing GFRAL belong to a small part of the brain outside the barrier, J?rgensen and colleagues believe they have a good drug target.
, the team created mice that could not produce GFRAL receptors and compared them to conventional mice.
when the researchers fed them high-fat foods for 16 weeks, the weight of all mice doubled, from about 20 grams to 40 grams.
received daily GDF15 injections for four weeks in a row, reducing the food intake of regular mice and thus helping them lose 5 to 10 grams.
this accounts for a large part of the overall weight.
mice without GFRAL receptors did not show weight loss after receiving GDF15 injections, but others behaved similarly to conventional mice.
another mouse experiment, receiving a higher dose of GDF15 a day resulted in a 75 percent reduction in food intake in mice, from 20 grams to 5 grams per day.
diet was restricted to the same amount of food but did not receive GDF15 injections and lost a similar amount of weight and fat.
supports the idea that GDF15 works primarily by suppressing appetite rather than boosting metabolism and burning calories.
, also published in the journal Nature Medicine, identified GFRAL as a receptor to GDF15 and obtained similar results that inhibited diet.
the study was conducted by Indianapolis-based Lile and San Diego-based Jason Biotherapy.
addition, Jensen researchers created a long-term version of GDF15 and injected it into monkeys.
it remained active in the monkey's bloodstream for four weeks and helped it lose 4% of its body weight.
"We are pleased to see that the main findings of all three articles are consistent.
," said Xinle Wu, who led the study at Lilly.
potential concern about GDF15 is that it works on the brain's vomiting-induced centers.
Jensen did not observe signs of nausea, anxiety or vomiting when they were given GDF15 in monkeys.
, however, says Richard Palmiter, a neuroscientologist at the University of Washington who studies appetite regulation, "because you can't ask animals how they feel, there's a risk that drugs will make humans feel uncomfortable rather than full."
so far, mr J?rgensen said his team had not noticed any side effects from GDF15.
often occur when the drug binds to multiple targets or when receptors spread throughout the body.
so far, GDF15 appears to be selective about GFRAL, which itself is confined to two smaller brain regions.
he also said Noel and Nord were making small adjustments to the GDF15 to have a stronger and longer-lasting impact.
the improved protein may be tested in human clinical trials, all three companies will keep their schedules open.
J?rgensen predicts that GDF15-based drugs combine with existing or potential future weight-loss treatments to produce the best results.
.