Apelin inhibits diet-induced obesity by enhancing lymphatic and blood vessel integrity.
Angiogenesis is tightly associated with the outgrowth of adipose tissue, leading to obesity, which is a risk factor for type 2 diabetes and hypertension, mainly because expanding adipose tissue requires an increased nutrient supply from blood vessels. Therefore, induction of vessel abnormality by adipokines has been well studied, whereas how altered vascular function promotes obesity is relatively unexplored. Also, surviving Prox1 heterozygous mice showed abnormal lymphatic patterning and adult-onset obesity, indicating that accumulation of adipocytes could be closely linked with lymphatic function. Here we propose a new anti-obesity strategy based on enhancement of lymphatic and blood vessel integrity with apelin. Apelin-knockout mice given a high-fat diet showed an obese phenotype associated with abnormal lymphatic and blood vessel enlargement. Fatty acids present in the high-fat diet induced hyperpermeability of endothelial cells, causing adipocyte differentiation, whereas apelin promoted vascular stabilization. Moreover, treatment of high-fat-diet-fed apelin-knockout mice with a selective cyclooxygenase-2 inhibitor, celecoxib, improved vascular function, and also attenuated obesity. Finally, apelin transgenic mice showed decreased subcutaneous adipose tissue owing to inhibition of high-fat-diet-induced hyperpermeability of vessels. These results indicate that apelin inhibits high-fat-diet-induced obesity by enhancing vessel integrity. Apelin could serve as a therapeutic target for treating obesity and related diseases.
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GENE-Y GENE-Y CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y
Apelin Apelin celecoxib Fatty acids apelin cyclooxygenase-2 apelin Apelin adipokines Prox1 apelin