a multitarget angiogenesis inhibitor, ctt peptide-endostatin mimic-kringle 5, prevents diet-induced obesity

Adipose tissue vasculature has been considered an attractive target for prevention and treatment of obesity. aarp (ctt peptide-endostatin mimic-kringle 5) is a novel multitarget fusion protein against tumor angiogenesis. this study aimed to examine the effects of aarp on diet-induced obesity and its possible molecular mechanism. treatment with aarp markedly prevented weight gains, improved metabolic disturbances, and decreased adipose tissue angiogenesis in diet-induced obese mice without noticeable toxicities. in addition to its potent antiangiogenic and mmp-2/9 inhibitory activities, aarp administration also significantly increased energy expenditure, influenced the metabolic and angiogenic gene expression profiles, and attenuated obesity-induced inflammation, demonstrating its systemic beneficial effects. importantly, aarp exhibited no effect on mice fed with standard normal mouse diet. furthermore, the aarp-treated hfd-fed mice experienced a significant increase in lifespan during the posttreatment observation period, compared with untreated hfd-fed mice. our results suggest that aarp might be pharmacologically useful for treatment of obesity or obesity-related metabolic disorders in humans. what is already known • more effective and safe therapies for obesity are in urgent need. • aarp is a novel multitarget fusion protein against tumor angiogenesis. what this study adds • aarp prevents obesity, improves metabolic disorders in mice fed high-fat diet. • aarp increases energy expenditure, decreases adipose tissue angiogenesis, and increases lifespan. • aarp is well tolerated and exhibits no observable toxicity. clinical significance • aarp be a promising therapeutic agent against obesity or obesity-related metabolic disturbances.