Fibro-Adipogenic Remodeling of the Diaphragm in Obesity-Associated Respiratory Dysfunction

摘要: Respiratory dysfunction is a common complication of obesity, conferring cardiovascular morbidity and increased mortality often necessitating mechanical ventilatory support. While impaired lung expansion in the setting adipose mass reduced central response to hypercapnia have been implicated as pathophysiological drivers, impact obesity on respiratory muscles-in particular, diaphragm-has not investigated detail. Here, we demonstrate that chronic high-fat diet (HFD) feeding impairs diaphragm muscle function, assessed vivo by ultrasonography ex measurement contractile force. During an HFD time course, progressive tissue collagen deposition within parallel deficits. Moreover, intradiaphragmatic fibro-adipogenic progenitors (FAPs) proliferate with long-term while giving rise adipocytes type I collagen-depositing fibroblasts. Thrombospondin 1 (THBS1), circulating adipokine, increases induces FAP proliferation. These findings suggest novel role for FAP-mediated remodeling obesity-associated dysfunction.