Endostatin Prevents Dietary-Induced Obesity by Inhibiting Adipogenesis and Angiogenesis

Area of Science:

• Biochemistry
• Metabolic disease research
• Molecular biology

Background:

• Angiogenesis inhibition is a studied obesity target.
• Endostatin's effects on adipogenesis and obesity were previously unknown.
• Adipogenesis is crucial for regulating adipocyte number, body weight, and metabolic health.

Purpose of the Study:

• To investigate the inhibitory effect of endostatin on adipogenesis and dietary-induced obesity.
• To elucidate the molecular mechanism underlying endostatin's anti-adipogenic activity.
• To explore the combined roles of adipogenesis and angiogenesis inhibition in endostatin's anti-obesity effects.

Main Methods:

• Investigated endostatin's interaction with Sam68 RNA-binding protein in preadipocytes.
• Analyzed the impact of this interaction on mammalian target of rapamycin (mTOR) gene expression and pathway activity.
• Assessed endostatin's effect on dietary-induced obesity and related metabolic disorders in vivo.

Main Results:

• Endostatin inhibits adipogenesis by interfering with Sam68 binding to mTOR intron 5.
• This interaction leads to reduced mTOR expression and impaired mTOR complex 1 pathway activity.
• Endostatin treatment prevented dietary-induced obesity, insulin resistance, glucose intolerance, and hepatic steatosis.

Conclusions:

• Endostatin effectively inhibits adipogenesis and dietary-induced obesity.
• Its mechanism involves disrupting Sam68-mTOR interaction, impacting adipogenesis.
• Endostatin's combined anti-angiogenic and anti-adipogenic properties suggest potential for treating obesity and metabolic syndromes.