Investigating the Sex‐Based Differences in Lung Inflammation in an Obesity Model of Early Sepsis

Background Sepsis is a life‐threatening response to infection and the most common organ to fail is the lung. There is clinical data to support that obese individuals with sepsis may have a survival advantage. We have previously shown that male obese mice have reduced lung injury during early sepsis. There are sex differences in the response to sepsis with women generally having better outcomes. The objective of this study was to determine if obese female mice were also protected from sepsis‐induced lung inflammation. Methods 5 week old female C57BL/6 mice, housed in static cages, were randomized to either a high fat Western diet (HFD) (n=12) (Modified Breslow Dyets510151) or normal chow diet (NCD) (n=14) for 15 weeks. Diet restriction to 70% of normal intake was introduced gradually after 6 weeks of ad lib access to control the weight gain of the NCD group. Glycemic control was compared between groups at 14 weeks by a glucose tolerance test where mice were fasted for 6 hours then given 2 g/kg of 20% glucose solution IP follow by glucose measurements at 15, 30, 60 and 120 minutes. At 20 weeks of age sepsis was induced by cecal ligation and puncture with a single 18 ga puncture. All mice received 2 mls of Ringer's lactate subcutaneously prior to surgery and 500 ml immediately post‐surgery and 4 hours later. Animals were euthanized at 6 hrs and tissues and blood collected. Airway inflammation was assessed by quantifying lung myeloperoxidase activity in snap‐frozen lung tissue. Results Female mice fed the HFD diet gained significantly more weight (31.9 ± 1.9 (SE) g compared to 20.9 ± 0.8 g) and had larger livers (1.8 ± 0.2 g vs 0.8 ± 0.04g) compared to the NCD mice. HFD female also had higher glucose levels (peak 24.8 ± 1.8 mmol/l) compared to NCD (peak 16.6 ± 1.6 mmol/l) following a glucose challenge. WBC counts of HFD (1.1 ± 0.1 ×10 9 /l) and NCD (1.1 ± 0.1 ×10 9 /l) septic mice were significantly lower the sham operated mice (HFD 2.7 ± 0.2 ×10 9 /l vs NCD 2.0 ± 0.2 ×10 9 /l). In contrast to our previous findings in septic male mice, there were no significant differences observed in lung myeloperoxidase levels between the HFD and NCD female mice (24.1 ± 2.0 U/mg tissue compared to 27.6 ± 1.6 U/mg tissue). Conclusions In female mice fed a HFD weight gain is associated with glucose intolerance. In contrast to our published work in male mice, female obese mice gain significantly less weight and have smaller livers than their male counterparts. Importantly, obesity conferred no protection from early sepsis‐induced lung inflammation compared to NCD fed septic female mice. Support or Funding Information Funded from an internal funds administered by the Department of Medicine This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

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