Once-Heralded Obesity Research Called into Question

UC scientists might have dashed hopes for a new, natural weight-loss treatment reported recently by British researchers.

The UC Medical Center team says that repeated studies have failed to reproduce the findings, claimed in the British report, that the gastrointestinal hormone PYY3-36 decreases appetite and weight gain in rodents.

When the British scientists first published their report in the leading scientific journal Nature in August 2002, it generated excitement worldwide about the potential of PYY3-36 in treating obesity. Several companies moved to bring this natural treatment to market.

Now, in a rebuttal in Nature's "Brief Communications Arising" section (July 8, 2004), the Cincinnati scientists report that 42 investigators from 15 international institutions have been unable to reproduce the findings.

Matthias Tschoep, MD, of the Obesity Research Center at the UC Genome Research Institute, who led the latest research, says the original report by Dr. Rachel Batterham and her colleagues at Imperial College Faculty of Medicine, London, "was heralded as potentially offering a new therapy for obesity."

"Our original aim was to take Dr. Batterham's results and work to accelerate the process toward a new treatment option for obesity," said Dr. Tschoep.  "The results we generated were entirely unexpected.

"We have been unable to replicate these results. Although the reasons for this discrepancy remained undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations."

The UC Medical Center team conclude: "To our knowledge, only one group not associated with the authors has so far replicated parts of the original study.  However, this group found no effect of PYY3-36 on body weight or on chronic food intake, and no effect on acute food intake without specific pre-fasting."

Dr. Tschoep said he and his colleagues don't exclude the possibility that some specific-but yet unknown-experimental conditions might be required to reproduce the appetite-inhibiting effect of PYY3-36.

However, he says, "We feel it's our  responsibility to share the results of our  numerous studies with patients and doctors fighting obesity, as well as with fellow scientists facing the difficult decision as to which molecular target they should invest their limited resources in, or which drug may justify expensive clinical trials."

UC co-authors include Randy Seeley, PhD, and Stephen Benoit, PhD, both of the Obesity Research Center at UC's Genome Research Institute.

A summary of the group's findings is published in the July 8 Nature, and full details are available online at

www.pyyobesity.com

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