S-030 | Metabolic Rhythms in Time-Dependent Severity of Septic Mice

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

Camila Senna^1°, Malena Mul Fedele^2°, Ignacio Aiello^3°,  Guido Hokama^1°, Diego Golombek^4°, Natalia Paladino^1°

^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° Integrated Cellular Responses laboratory, Fralin Biomedical Research Institute, Virginia Tech Carilion, Roanoke, USA.
^4° Laboratorio Interdisciplinario del Tiempo (LITERA), Universidad de San Andrés, Buenos Aires, Argentina.

Sepsis, a syndrome caused by dysregulated host response to pathogens, is a leading cause of death from infection. Patients with sepsis present early metabolic alterations that disturbs homeostasis and affects glycemic control. In murine models, sepsis mortality is strongly influenced by the circadian system: mice inoculated with high doses of lipopolysaccharide (LPS) at the end of the day exhibit higher mortality rate (~80%) than those inoculated in the middle of the night (~30%). Our previous results revealed that proteins differentially upregulated in serum from mice injected with LPS at ZT19 (ZT0: lights on; ZT12: lights off) are mainly associated with glucose and lipid metabolism.
To further study the differences in metabolism, we evaluated blood glucose levels after stimulus at ZT11 and ZT19. We observed blood glucose levels significantly increased after LPS administration only at ZT11. To study how glycemic response affects sepsis severity, we inhibited the hyperglycemic response by metformin administration before LPS at ZT11, and simulated the hyperglycemic response by exogenous glucose administration after LPS at ZT19. Both manipulation result in decreased severity. These results show time-differences in glucose metabolism in response to LPS, which generates early hyperglycemia associated with higher severity. During the resting phase, elevated blood glucose contributes to a worse prognosis, while during the active phase, efficient glucose metabolism improves outcom.