Development of a Murine Model of Early Sepsis in Diet-Induced Obesity

Khan, Momina; Patrick, Amanda L.; Fox‐Robichaud, Alison

doi:10.1155/2014/719853

Cited by 12 publications

(11 citation statements)

References 34 publications

(41 reference statements)

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“…Multiple studies demonstrate that obesity increases inflammation and mortality in sepsis models . Other studies utilizing longer feeding strategies showed contradictory findings and demonstrate a protective effect of obesity during sepsis . The impact of obesity on the outcomes from sepsis remains unclear but may be affected by the duration of high‐fat feeding.…”

Section: Discussionmentioning

confidence: 99%

“…Previous work from our laboratory demonstrated that short‐term (3 weeks), high‐fat diet (HFD)‐fed mice had more inflammation and higher mortality following sepsis compared with normal diet (ND)‐fed mice . Other studies have shown contradictory findings on obesity‐associated mortality after sepsis in that prolonged exposure to HFD led to protection of sepsis‐induced lung injury . Mice fed a 12‐week HFD became obese and hyperleptinemic and had improved survival after polymicrobial sepsis .…”

Section: Introductionmentioning

confidence: 94%

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Obesity enhances sepsis‐induced liver inflammation and injury in mice

Kaplan

Nowell

Lahni

et al. 2016

Obesity

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Objective How obesity affects the response to sepsis is not completely understood. We hypothesize that obesity alters adipose and hepatic tissue inflammation through STAT3 activation. Methods Male C57BL/6 mice at six-weeks of age were randomized to a high-fat (HFD) (60% kcal fat) or normal diet (ND) (16% kcal fat) for 6–7 weeks. Sepsis was then induced by cecal ligation and puncture (CLP) and animals were monitored for survival or sacrificed and tissue collected. Results HFD-fed mice gained more weight, had increased fat mass and were glucose intolerant compared to ND-fed mice. Obesity increased hepatic neutrophil infiltration and injury after sepsis. Obese mice had higher plasma leptin levels compared to non-obese mice. Adipose tissue expression of adiponectin receptor 2, TNFα and PPARγ were altered during sepsis and affected by obesity but the greatest change in adipose tissue expression was in leptin. Septic obese mice had lower plasma IL-17a, IL-23 and TNFα levels and increased hepatic STAT3 and Activator Protein-1 activation compared to non-obese septic mice. Ultimately, obese mice had a lower probability of survival following sepsis. Conclusions Obese mice are more susceptible to sepsis and have higher mortality, in part, through activation of the STAT3 signaling pathway and through AP-1 activation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Obesity enhances sepsis‐induced liver inflammation and injury in mice

Kaplan

Nowell

Lahni

et al. 2016

Obesity

View full text Add to dashboard Cite

show abstract

“…The results from animal studies have been far from consistent with regard to these variables. Many have shown that obesity increases cytokine expression during sepsis (12, 32, 64, 69), while others have shown either no difference or decreased levels of cytokines in obese animals (36, 73). In CLP models of sepsis, obese mice were found to have increased leukocyte and platelet adhesion in the microcirculation of the brain (83, 84) and intestines (74), creating a more prothrombogenic environment.…”

Section: Obesity and Animal Models Of Critical Illnessmentioning

confidence: 99%

Obesity and Critical Illness

Mittwede

Clemmer

Bergin

et al. 2016

Shock

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Critical illness is a major cause of morbidity and mortality around the world. While obesity is often detrimental in the context of trauma, it is paradoxically associated with improved outcomes in some septic patients. The reasons for these disparate outcomes are not well understood. A number of animal models have been used to study the obese response to various forms of critical illness. Just as there have been many animal models that have attempted to mimic clinical conditions, there are many clinical scenarios that can occur in the highly heterogeneous critically ill patient population that occupies hospitals and intensive care units. This poses a formidable challenge for clinicians and researchers attempting to understand the mechanisms of disease and develop appropriate therapies and treatment algorithms for specific subsets of patients, including the obese. The development of new, and the modification of existing animal models is important in order to bring effective treatments to a wide range of patients. Not only do experimental variables need to be matched as closely as possible to clinical scenarios, but animal models with pre-existing comorbid conditions need to be studied. This review briefly summarizes animal models of hemorrhage, blunt trauma, traumatic brain injury, and sepsis. It also discusses what has been learned through the use of obese models to study the pathophysiology of critical illness in light of what has been demonstrated in the clinical literature.

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“…MPO activity was measured as previously described. 20 Analysis of murine PC, APC, TAT, and IL-6 levels Mouse PC and APC was assayed as described previously. 17 Mouse thrombinantithrombin (TAT) complexes were measured using the Enzygnost TAT kit as described by the manufacturer (Siemens).…”

Section: Lps Challengementioning

confidence: 99%