067 | Differences in metabolic pathways are associated with time-dependent severity in septic mice


Author: Camila Agustina Senna | Email: camilaagustinasenna@gmail.com

Camila A. Senna , Malena L. Mul Fedele , Ignacio Aiello , Diego Golombek , Natalia Paladino

1° Laboratorio de Cronobiología, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes/CONICET, Buenos Aires, Argentina
2° Laboratorio de Cronofisiología, Instituto de Investigaciones Biomédicas/UCA-CONICET, Buenos Aires, Argentina
3° Laboratorio Interdisciplinario del Tiempo (LITERA), Universidad de San Andrés, Buenos Aires, Argentina

Sepsis is a syndrome caused by a dysregulated host response to pathogens, representing the leading cause of death from infection. In murine models, mortality rates largely depend on the circadian system. Mice intraperitoneally inoculated with high doses of lipopolysaccharide (LPS; 20 mg/kg) at the end of the day exhibit a higher mortality rate (~80%) than those inoculated at the middle of the night (~30%), along with a worse inflammatory response and hypothermia. To study the mechanisms involved in this daily variation, we conducted a proteomic analysis on serum samples collected 2 hours after LPS inoculation at both time of the day. We observed that proteins increased at the middle of the night are related to glucose metabolism, energy utilization, and lipid metabolism. On the other hand, differentially expressed proteins at the end of the day are involved in the inflammatory response, oxidative stress, and cellular communication, migration, and adhesion. Additionally, we evaluated glycemia after stimulation at both time points and found that animals exhibit pronounced hyperglycemia in response to LPS within 2 hours after the stimulus, only in mice stimulated at the end of the day. In conclusion, LPS triggers different metabolic responses based on timing of the stimulus. Moreover, the increase in blood glucose levels in response to LPS at the end of the day may signal centrally and/or promote the activation of the inflammatory response, leading to increased severity.