title: Endostatin Prevents Dietary-Induced Obesity by Inhibiting Adipogenesis and Angiogenesis.
abstract: Endostatin is a well-known angiogenesis inhibitor. Although angiogenesis has been considered as a potential therapeutic target of obesity, the inhibitory effect of endostatin on adipogenesis and dietary-induced obesity has never been demonstrated. Adipogenesis plays a critical role in controlling adipocyte cell number, body weight, and metabolic profile in a homeostatic state. Here we reveal that endostatin inhibits adipogenesis and dietary-induced obesity. The antiadipogenic mechanism of endostatin lies in its interaction with Sam68 RNA-binding protein in the nuclei of preadipocytes. This interaction competitively impairs the binding of Sam68 to intron 5 of mammalian target of rapamycin (mTOR), causing an error in mTOR transcript. This consequently decreases the expression of mTOR, results in decreased activities of the mTOR complex 1 pathway, and leads to defects in adipogenesis. Moreover, our findings demonstrate that the antiangiogenic function of endostatin also contributes to its obesity-inhibitory activity. Through the combined functions on adipogenesis and angiogenesis, endostatin prevents dietary-induced obesity and its related metabolic disorders, including insulin resistance, glucose intolerance, and hepatic steatosis. Thus, our findings reveal that endostatin has a potential application for antiobesity therapy and the prevention of obesity-related metabolic syndromes.
authors.affiliation: National Engineering Laboratory of Anti-tumor Protein Therapeutics, Beijing Key Laboratory of Protein Therapeutics, and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory of Anti-tumor Protein Therapeutics, Beijing Key Laboratory of Protein Therapeutics, and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: National Engineering Laboratory of Anti-tumor Protein Therapeutics, Beijing Key Laboratory of Protein Therapeutics, and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Xin-an
authors.initials: XA
authors.lastname: Lu
authors.affiliation: National Engineering Laboratory of Anti-tumor Protein Therapeutics, Beijing Key Laboratory of Protein Therapeutics, and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Liu
authors.affiliation: National Engineering Laboratory of Anti-tumor Protein Therapeutics, Beijing Key Laboratory of Protein Therapeutics, and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.affiliation: National Engineering Laboratory of Anti-tumor Protein Therapeutics, Beijing Key Laboratory of Protein Therapeutics, and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing, China yluo@tsinghua.edu.cn.
authors.forename: Yongzhang
authors.initials: Y
authors.lastname: Luo
mesh_terms: D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D059305:Diet, High-Fat; D043169:Endostatins / Q000494:pharmacology*; D007438:Introns; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors; D009765:Obesity / Q000517:prevention & control*; D016601:RNA-Binding Proteins / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020533:Angiogenesis Inhibitors; D043169:Endostatins; C513253:Khdrbs1 protein, mouse; D046912:Multiprotein Complexes; D016601:RNA-Binding Proteins; C546843:mTOR protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases