Diaphragmatic function is enhanced in fatty and diabetic fatty rats.
BACKGROUND
Obesity 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.


METHODS
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. We analyzed diaphragm morphology, cytokines, and protein expression of the protein kinase signaling pathways.


RESULTS
Diaphragm 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.


CONCLUSIONS
Diaphragmatic 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.
Sorbonne Universités UPMC Univ Paris 06, UMR INSERM-UPMC 1166, IHU ICAN, Paris, France.|Department of Anesthesiology and Critical Care Medicine, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.|Department of Anesthesia and Critical Care B, Hôpital Saint-Eloi, CHU de Montpellier, France.
Audrey
http://orcid.org/0000-0002-3413-2752
A
De Jong
Sorbonne Universités UPMC Univ Paris 06, UMR INSERM-UPMC 1166, IHU ICAN, Paris, France.|Department of Anesthesiology and Critical Care Medicine, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
Serge
S
Carreira
Sorbonne Universités UPMC Univ Paris 06, UMR INSERM-UPMC 1166, IHU ICAN, Paris, France.|Department of Emergency Medicine and Surgery, Hôpital Pitié-Salpêtrière, APHP, Paris, France.
Na
N
Na
Sorbonne Universités UPMC Univ Paris 06, UMR INSERM-UPMC 1166, IHU ICAN, Paris, France.|Department of Anesthesiology and Critical Care Medicine, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
Aude
A
Carillion
Sorbonne Universités UPMC Univ Paris 06, UMR INSERM-UPMC 1166, IHU ICAN, Paris, France.|Emergency Department, Zonghnan University Hospital, Wuhan University, Wuhan, The People's Republic of China.
Cheng
C
Jiang
Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, Paris, France.
Maud
M
Beuvin
Department of Endocrinologic and Oncologic Biochemistry, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
Jean-Marc
JM
Lacorte
Sorbonne Universités UPMC Univ Paris 06, UMR INSERM-UPMC 1166, IHU ICAN, Paris, France.|Department of Metabolic Biochemistry, Hôpital Pitié-Salpêtrière, APHP, Paris, France.|Université Paris Descartes, Faculty of Pharmacy, Paris, France.
Dominique
D
Bonnefont-Rousselot
Sorbonne Universités UPMC Univ Paris 06, UMR INSERM-UPMC 1166, IHU ICAN, Paris, France.|Department of Emergency Medicine and Surgery, Hôpital Pitié-Salpêtrière, APHP, Paris, France.
Bruno
B
Riou
Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, Paris, France.
Catherine
C
Coirault
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology*; D003964:Diaphragm / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D011446:Prospective Studies; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction / Q000502:physiology
D027501:Monocarboxylic Acid Transporters; D051057:Proto-Oncogene Proteins c-akt