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.
Highlights
Obesity is associated with a decrease in mortality in the intensive care unit (ICU)
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
Obesity is frequently associated with type II diabetes which further increases the causes of mortality via microvascular and macrovascular complications
Summary
Diaphragm 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. Experiments were conducted in accordance with the Principles of Laboratory Animal Care (NIH publication N0 ̊ 86–23, revised 1985) in an authorized laboratory under supervision of authorized researchers (CC, AC). The care and handling of the animals were in accord with National Institutes of Health guidelines. The project had been approved by the Institutional Animal Care and Use Committee through the French Ministry of Higher Education and Research (Comite Regional d’Ethique en Experimentation Animale Paris-Comite 3, Paris, France, agreement number: 02579.02). Diaphragm force in fatty and diabetic fatty rats Animals. Rats were purchased from Charles River (Saint Germain sur l’Arbresle, France) and cared in a labeled housing place (agreement number B-75-13-08) with food and water ad libitum. A proportion of these animals were used in another experimental study assessing the β-adrenergic function of the myocardium [19]
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