Visfatin study retracted from Science

Osaka researchers retract disputed paper but claim results are valid

Oct 25, 2007
Jonathan Scheff
The authors of a controversial 2004 study in Science describing visfatin, a fat cell protein with insulin-mimetic properties, are retracting their findings in a letter published online today (October 25) but maintain that the findings are valid.Atsunori Fukuhara and his colleagues at the University of Osaka wrote in the retraction letter, "At the suggestion of the editor of Science, we have agreed to retract the paper, even though we continue to stand by our conclusions." In the study, which has been cited more than 200 times, the researchers identified visfatin as a new protein found in adipose tissue that has insulin-mimetic properties. After the paper was published online in December 2004, other research showed visfatin to be genetically identical to a known growth factor called pre-B cell colony-enhancing factor (PBEF). Researchers have also cast doubt on whether it is in fact insulin-mimetic.Masaya Tohyama, dean of the Osaka University Graduate School of Medicine, told the research group to retract their paper last June, after the school conducted a year-long investigation of the findings. According to Science, the school did not allege scientific misconduct, but raised "numerous questions" about the research, such as the exclusion of female heterozygous knockout mice from the data set. But the researchers refused at the time to retract the paper, and corresponding author Iichiro Shimomura said the group would take "adequate action" against the university."After receiving the reports of Osaka University Medical School, Science journal judged and recommended us to retract the paper by the authors' agreement," Shimomura told The Scientist in an Email. "We authors discussed the situation many times, and decided to retract the paper for ourselves."In his Email, Shimomura noted two errors that the authors acknowledge: The use of 125I-labeled visfatin with low specific radioactivity and a descriptive mistake in the legend of figure 4I, which concerns the binding of insulin and visfatin to HEK-293 cells."We authors admitted that we could increase the integrity of the data by using higher specific activity of radio-labeled protein," he wrote, adding that the descriptive mistake "decreased the integrity of the contents of the paper.""Visfatin/PBEF is recognized as an inflammatory protein," Alessandro Doria of Harvard's Joslin Diabetes Center told The Scientist. Based on his own research on the visfatin gene, Doria conjectures that an increase in visfatin is associated with an increase in inflammation, which in turn predisposes to type II diabetes. "This seems to be in contrast to visfatin having an insulin-mimetic action," he said."Whatever the reason is, they finally did the right thing," said Shin-ichiro Imai of the Washington University School of Medicine in St Louis, whose upcoming paper on the functionality of visfatin/PBEF contradicts the Fukuhara group's finding of insulin-mimetic properties. "Investigators in academia and industry were unable to reproduce their results," he said. In their retraction, however, the Fukuhara group noted that "another laboratory recently reported that visfatin has insulin mimetic effects in cultured osteoblasts."Tohyama wrote in Email to The Scientist, "Unfortunately we don't have further information about the issue now." A representative of Science said only: "Based on our evaluation of the report, we felt that this was the appropriate course of action."In today's letter to Science, the Fukuhara group wrote: "Thus far, we have found four different lots of purified recombinant visfatin protein that have both adipogenic and insulin mimetic activities ... We are willing to send them to other investigators for independent validation. We are continuing to investigate the significance of this molecule."Jonathan Scheff mail@the-scientist.comLinks within this article:K. Chi, "What is visfatin?", The Scientist, June 26, 2007. http://www.the-scientist.com/news/display/53297/A. Fukuhara et al, "Visfatin: a protein secreted by visceral fat that mimics the effects of insulin," Science, Jan. 21, 2005 (print), Dec. 16, 2004 (online). http://www.the-scientist.com/pubmed/15604363A. Fukuhara et al, retraction of "Visfatin: a protein secreted by visceral fat that mimics the effects of insulin," Science, Dec. 25, 2007. http://www.sciencemag.org/G. Flores, "Insulin mimic found in fat," The Scientist, Dec. 17, 2004. http://www.the-scientist.com/article/display/22541/B. Samal et al, "Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor," Molecular and Cellular Biology, Feb. 1994. http://www.the-scientist.com/pubmed/8289818C. Hug and H. Lodish, "Visfatin: A New Adipokine," Science, Jan. 21, 2005. http://www.the-scientist.com/pubmed/15604359D. Normile, "Osaka University Researchers Reject Demand to Retract Science Paper," Science, June 22, 2007. http://www.the-scientist.com/pubmed/17588905Alessandro Doria http://www.hsph.harvard.edu/faculty/alessandro-doria/G. Flores, "New adipocytokine found," The Scientist, Jan. 17, 2005. http://www.the-scientist.com/article/display/15186/Shin-ichiro Imai http://dbbs.wustl.edu/H. Xie et al, "Insulin-like effects of visfatin on human osteoblasts," Calcified Tissue International, March 2007. http://www.the-scientist.com/pubmed/17340225