Diaphragmatic function is enhanced in fatty and diabetic fatty rats

Abstract

BackgroundObesity is associated with a decrease in mortality in the intensive care unit (ICU) (the "obesity paradox"). We hypothesized that obesity may paradoxically improve diaphragmatic function.MethodsDiaphragm contractility was prospectively recorded in vitro in adult male Zucker lean (control), fatty, and diabetic fatty rats, at rest, after 12h mechanical ventilation and after fatigue. We analyzed diaphragm morphology, cytokines, and protein expression of the protein kinase signaling pathways.ResultsDiaphragm active-force (AF) was higher in fatty (96±7mN.mm-2,P = 0.02) but not in diabetic fatty rats (90±17mN.mm-2) when compared with controls (84±8mN.mm-2). Recovery from fatigue was improved in fatty and diabetic fatty groups compared with controls. Ventilator-induced diaphragmatic dysfunction was observed in each group, but AF remained higher in fatty (82±8mN.mm-2,P = 0.03) compared with controls (70±8mN.mm-2). There was neutral lipid droplet accumulation in fatty and diabetic fatty. There were shifts towards a higher cross-sectional-area (CSA) of myosin heavy chain isoforms (MyHC)-2A fibers in fatty and diabetic fatty compared with control rats (P = 0.002 and P<0.001, respectively) and a smaller CSA of MyHC-2X in fatty compared with diabetic fatty and control rats (P<0.001 and P<0.001, respectively). The phosphorylated total-protein-kinase-B (pAKT)/AKT ratio was higher in fatty (182±58%,P = 0.03), but not in diabetic fatty when compared with controls and monocarboxylate-transporter-1 was higher in diabetic fatty (147±36%,P = 0.04), but not in fatty.ConclusionsDiaphragmatic force is increased in Zucker obese rats before and after mechanical ventilation, and is associated with activation of AKT pathway signaling and complex changes in morphology.

ARDS in Obese Patients: Specificities and Management

“…The type of obesity (grade, repartition of fat [android vs. gynoid], sarcopenic/non-sarcopenic obesity) is not indicated and muscular strength and function and the metabolic status of the patients (insulin sensitivity) were not evaluated. Diaphragmatic force may also be stronger in obese patients, as recently suggested by an experimental study performed in obese Zucker rats [26]. In obese rats, the diaphragmatic force was increased at baseline and after mechanical ventilation, compared to non-obese rats, which might be a protective factor in case of ARDS onset, facilitating liberation from mechanical ventilation.…”

Risk factors and outcomes for airway failure versus non-airway failure in the intensive care unit: a multicenter observational study of 1514 extubation procedures

“…Female sex was also found as a risk factor for post-extubation stridor in previous studies, probably resulting from small airway size and a large endotracheal tube size in relation to laryngeal size [ 45 , 46 ]. Obesity might be associated with a better prognosis in both acute respiratory distress syndrome [ 47 ] and overall for ICU patients [ 48 ]. The “obesity paradox” also seems present after extubation, and more accurately in non-airway failure following extubation.…”

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

“…Preclinical studies of respiratory function in obesity have largely employed genetically obese Zucker diabetic fatty (ZDF) rats. In this model, ex vivo diaphragmatic testing has yielded equivocal results, with contractile force reduced in older animals (8) but unchanged (9,10) or increased (11) in younger animals. ob/ob mice demonstrate hypoventilation reversible by leptin infusion, indicating that this adipokine may regulate central respiratory drive (12).…”