Endocrine Abstracts

Introduction: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis, a phenomenon called obesity paradox has been described, which involves a reduction in mortality in patients with a body mass index allowing for the diagnosis of overweight and obesity. In the clinical context, the phenomenon is confirmed by current meta-analyses. The aim of the study is a systematic review and meta-analysis of studies on obesity paradox conducted on an animal model of sepsis.

Methods: A search was performed on PubMed for articles published up to December 31, 2023. Studies examining obesity-related mortality in a murine model of sepsis were selected.

Results: We identified 19 studies that reported sepsis mortality data from 36 experiments. Obesity was obtained in the diet-induced obesity model or in the leptin deficiency model. Sepsis was induced in the cecal ligation and puncture, cecal slurry injection, lipopolysaccharide injection or Staphylococcus aureus inoculation models. In the studies, obesity in the experimental groups (obesity model) was, depending on the study, higher or lower than in the control groups. Nine studies using the same obesity model (diet-induced obesity) and sepsis model (cecal ligation and puncture) were selected for meta-analysis. There was no statistically significant difference between animals receiving a high-fat diet and animals from the control group receiving a standard diet (P=0.5716). The statistical regression analysis showed that a higher age at the time of introduction of a high-fat diet (P<0.001) and a longer duration of feeding with a high-fat diet (P<0.001) reduce mortality, while a higher age (P<0.001) at the time of sepsis induction increases mortality. In the above model, the regression coefficient R² is 0.86 (P<0.001).

Conclusions: The results indicate the role of study protocol in the obtained results. The age of the animals at particular stages of the study and the duration of use of the high-fat diet may be important for the obtained results. Further research is necessary to confirm and better understand this phenomenon.