title: Development of a murine model of early sepsis in diet-induced obesity.
abstract: Sepsis, a global health issue, is the most common cause of mortality in the intensive care unit. The aim of this study was to develop a new model of sepsis that investigates the impact of prolonged western diet (WD) induced obesity on the response to early sepsis. Male C57BL/6 mice were fed either a high fat WD or normal chow diet (NCD) for 6, 15, or 27 weeks. Septic obese mice at 15 and 27 weeks had significantly lower levels of lung myeloperoxidase (26.3 ± 3.80 U/mg tissue) compared to age matched ad lib (44.1 ± 2.86 U/mg tissue) and diet restricted (63.2 ± 5.60 U/mg tissue) controls. Low levels of lung inflammation were not associated with changes in hepatic cytokines and oxidative stress levels. Obese mice had significantly (P < 0.0001) larger livers compared to controls. Histological examination of the livers demonstrated that WD fed mice had increased inflammation with pronounced fat infiltration, steatosis, and hepatocyte ballooning. Using this model of prolonged exposure to high fat diet we have data that agree with recent clinical observations suggesting obese individuals are protected from sepsis-induced lung injury. This model will allow us to investigate the links between damage to the hepatic microcirculation, immune response, and lung injury.
authors: Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, DBRI C5-106, 237 Barton Street East, Hamilton, ON, Canada L8L 2X2.
authors: Momina
authors: 0000-0002-1304-4593
authors: M
authors: Khan
authors: Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, DBRI C5-106, 237 Barton Street East, Hamilton, ON, Canada L8L 2X2.
authors: Amanda L
authors: AL
authors: Patrick
authors: Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, DBRI C5-106, 237 Barton Street East, Hamilton, ON, Canada L8L 2X2.
authors: Alison E
authors: AE
authors: Fox-Robichaud
authors: The Critical Care Translational Biology Group, 555 University Avenue RM 2830A, Toronto, ON, Canada M5G 1X8.
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D009765:Obesity / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D018805:Sepsis / Q000097:blood / Q000139:chemically induced / Q000473:pathology
chemical_list: D016207:Cytokines; D004041:Dietary Fats