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In This Issue of Diabetes

Mice fed a high-fat (60% fat) diet plus endostatin did not become obese or develop the equivalent obesityrelated diabetic complications at the same rate as mice given the same diet minus endostatin. That is the conclusion of Wang et al. in a study reported in this issue of Diabetes (p. 2442). Following up the animal studies, the researchers also detail relevant cell line studies that uncover specifi c mechanisms and cellular targets that endostatin might infl uence. Most importantly, the data point toward endostatin inhibiting both adipogenesis and angiogenesis and that together those processes might also have an antiobesity effect that is modifi ed via endostatin. The mechanisms detailed in the report suggest that endostatin fi rst interacts with the protein Sam68 in the nuclei of preadipocytes. This interaction appears to then competitively impair binding of the protein to mTOR (mechanistic/mammalian target of rapamycin), which ultimately leads to transcription errors and defects in adipogenesis. The biological and clinical signifi cance of these outcomes appear to be clear, according to author Dr. Yongzhang Luo, from Tsinghua University, Beijing, China: “Our data suggest that endostatin indirectly prevents adipogenesis by inhibiting angiogenic capacity of endothelial cells. Thus, endostatin may be an important mediator of the white adipose tissue microenvironment and obesity-related diabetic complications, which need to be investigated in the future. These fi ndings provide new insights into the biological relevance of this protein. We have also demonstrated that endostatin inhibits dietary-induced obesity and its related metabolic disorders. Although clinical trials of endostatin as an antitumor drug are not a good model to determine the effect of endostatin on body weight because of the combined use of endostatin and chemo drugs, it has been proven that endostatin is safe with rare untoward reactions or side effects and no drug resistance in these human clinical trials. Thus, endostatin has a great potential to be employed in antiobesity therapy and the prevention of obesity-related diabetic complications.”