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.

Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications

“…From both in vitro and in vivo experiments, they concluded that that endostatin may be able to effectively reduce the risk of developing insulin resistance, hepatic steatosis, and glucose intolerance by inhibiting the pathway of adipogenesis [238]. Adipogenesis plays a crucial role in determining the metabolic profile, the number of adipocytes, and body weight in the homeostatic state [238]. …”

Glucagon-like peptide 1 improves insulin resistance in vitro through anti-inflammation of macrophages

“…PCRs were performed in duplicates, and error bars in the charts represent the corresponding standard deviations. The primers used to detect mouse GLP-1R (22) were forward: 5′-TTG GGG TGA ACT TCC TCA TC-3′, reverse: 5′-CTT GGC AAG TCT GCA TTT GA-3′; β-actin (25) forward: 5′-GCC AAC CGT GAA AAG ATG ACC-3′, and reverse: 5′-CCC TCG TAG ATG GGC ACA GT-3′.…”

“…Transwell migration assay of macrophage was performed as previously described (25). Briefly, 2×10 5 RAW264 cells or mouse peritoneal macrophages transfected with scramble or GLP-1R siRNAs were supplemented with 100 μL serum-free medium and placed in the upper chamber with 8-mm pore size (BD Bioscience, USA) for migration assays, while 600 μL serum-free medium with or without LPS (200 ng/mL) were placed in the lower chamber.…”

“…Briefly, the 3T3-L1 preadipocytes were differentiated into adipocytes as described in a previous report (25). After differentiation, the medium was switched to low-glucose DMEM containing 0.3% bovine serum albumin (BSA) alone (control group) or with CM, CM-LPS, or CM-LPS-Ex4 and incubated at 37°C for 16 h. Then, the medium was switched to a KRBH buffer containing 10 nM of insulin with or without vehicles (DMSO), and with methanol and water extracts, and further incubated at 37°C for 30 min.…”

Biomarker-based Diagnosis and Personalized Medicine for Cancer Patients: Trinity of Nucleolin Guided, Endostatin Treatment, and Plasma Hsp90α Monitored

“…We have found that endostatin can prevent dietary-induced obesity by inhibiting adipogenesis and angiogenesis through interaction with Sam68 RNA-binding protein to paralyzing the mTOR pathway, which revealed that endostatin has a potential application for antiobesity therapy and prevention of obesity-related metabolic syndromes [75]. Another study in our lab reported for the first time that endostatin embedded novel ATPase activity, which mediates its antiangiogenic and antitumor activities [76].…”