Dataset Information

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

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

SUBMITTER: Buras ED

PROVIDER: S-EPMC6302533 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Buras Eric D ED Converso-Baran Kimber K Davis Carol S CS Akama Takeshi T Hikage Fumihito F Michele Daniel E DE Brooks Susan V SV Chun Tae-Hwa TH

Diabetes 20181025 1

Respiratory dysfunction is a common complication of obesity, conferring cardiovascular morbidity and increased mortality and often necessitating mechanical ventilatory support. While impaired lung expansion in the setting of increased adipose mass and reduced central response to hypercapnia have been implicated as pathophysiological drivers, the impact of obesity on respiratory muscles-in particular, the diaphragm-has not been investigated in detail. Here, we demonstrate that chronic high-fat di ...[more]

PMID: 30361289

Similar Datasets

Project description:BackgroundTransient diaphragm dysfunction is common during the first week after cardiac surgery; however, the precise incidence, risk factors, and outcomes of persistent diaphragm dysfunction are not well described.MethodsIn a single-centre prospective cohort study, we included all consecutive patients over 18 yr who underwent elective cardiac surgery. Diaphragm function was evaluated with ultrasound (M-mode) by recording the excursion of both hemidiaphragms at two different time points: preoperatively and after the seventh postoperative day in patients breathing without assistance. Significant diaphragm dysfunction after the seventh day of the index cardiac surgery was defined as a decrease in diaphragm excursion below the lower limit of normal: at rest, < 9 mm for women and < 10 mm for men; after a sniff test, < 16 mm for women and < 18 mm for men.ResultsOverall, 122 patients were included in the analysis. The median [interquartile range (IQR)] age was 69 [59-74] years and 96/122 (79%) were men. Ten (8%) patients had diaphragm dysfunction after the seventh postoperative day. We did not identify risk factors for persistent diaphragm dysfunction. Persistent diaphragm dysfunction was associated with a longer median [IQR] duration of noninvasive (8 [0-34] vs 0 [0-0] hr; difference in medians, 8 hr; 95% confidence interval [CI], 0 to 22; P < 0.001) and invasive mechanical ventilation (5 [3-257] vs 3[2-4] hr; difference in medians, 2 hr; 95% CI, 0.5 to 41; P = 0.008); a higher reintubation rate (4/10, 40% vs 1/112, 0.9%; relative risk, 45; 95% CI, 7.1 to 278; P < 0.0001), a higher incidence of pneumonia (4/10 [40%] vs 7/112 [6%]; relative risk, 6; 95% CI, 2 to 16; P < 0.001), and longer median [IQR] length of stay in the intensive care unit (8 [5-29] vs 4 [2-6] days; difference in medians, 4 days; 95% CI, 2 to 12; P = 0.002).ConclusionThe incidence of persistent diaphragm dysfunction was 8% in patients undergoing elective cardiac surgery and was associated with adverse respiratory outcomes.Study registrationClinicalTrials.gov (NCT04276844); prospectively registered 19 February 2020.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets