Submission ID 93394
| Poster Code | HR-P-88 |
|---|---|
| Title of Abstract | Ketone ester therapy as a novel approach to reduce systemic and organ inflammation and dysfunction in sepsis |
| Abstract Submission | Introduction: Sepsis is a dysregulated inflammatory response to an infection resulting in multi-organ injury. Currently, there are no effective treatments to reduce inflammation and prevent the inflammation-mediated damage during sepsis. Thus, new approaches are needed manage inflammation and improve patient outcomes. Herein, we tested the efficacy of a ketone therapy that increases circulating ketones via ketone esters. Ketones are small molecules produced by the liver in carbohydrate-deprived states, such as fasting. While ketones are classically known to be a metabolic source of energy, they also have non-metabolic effects, such as inhibiting inflammation. Thus, we hypothesized that ketones have anti-inflammatory effects which will protect against septic organ dysfunction and inflammation. Methods: 8-week-old mice orally received vehicle or ketone ester (KE) for 3 days. On day 3, mice received saline or lipopolysaccharide (LPS) to induce systemic inflammation and sepsis, and assessments were performed 24 hours post-injection. Results: LPS-treated mice had higher blood ketones compared to controls, suggesting that ketones may be an innate defense mechanism, and this response was further augmented in KE-treated septic mice. While LPS-treated mice had an induction of systemic pro-inflammatory cytokines (e.g., IL-1β, IL-6, interferon-γ) these cytokines were significantly lower in KE-treated septic mice. Similarly, LPS induced notable inflammation in the heart, kidney, and liver, most of which were reduced in KE-treated septic mice. LPS-induced cardiac dysfunction and renal fibrosis was also lower in KE-treated septic mice. Conclusion: Together, these data show that ketone therapy may be a novel approach to reducing inflammation and organ dysfunction in sepsis. |
| Please indicate who nominated you | Dr. Alan Underhill |
| What Canadian Institutes of Health Research (CIHR) institute is your research most closely aligned? | Circulatory and Respiratory Health Infection and Immunity |
| What Canadian Institutes of Health Research (CIHR) pillar of health research does your research fall under? | Biomedical |
| PDF of abstract | No file |
| Presenter and Author(s) | Shubham Soni Matthew Martens Shingo Takahara Heidi Silver Mourad Ferdaoussi Jason Dyck |
