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EFFECTS OF THE DUAL ADMINISTRATION OF HIGH-FAT DIET AND LIPOPOLYSACCHARIDE ON ANXIETY/DEPRESSIVE-LIKE BEHAVIOR AND HIPPOCAMPAL INFLAMMATORY MARKERS
Valentina Salaand 5 co-authors
Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC)
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS01-07AM-535
Presentation
Date TBA
Board: PS01-07AM-535
Event Information
Poster Board
PS01-07AM-535
Poster
View posterAbstract
Major Depressive Disorder (MDD) is a high-prevalence mood disorder affecting millions of people worldwide, especially women. Although the biological mechanisms underlying this disease remain unclear, both inflammation and obesity are known risk factors for developing MDD. Since the effect of the combination of these two factors is still poorly studied, we developed a double-hit model to evaluate the combined effect of obesity and inflammation on depression and anxiety, considering the possible sex-based differences.
C57BL/6 male and female mice were fed with normal chow or a High Fat Diet (HFD) for 5 weeks, followed by the acute administration of lipopolysaccharide (LPS): control, HFD, LPS and HFD+LPS groups. Behavioral tests were conducted to evaluate anxious- and depressive-like behaviors after the LPS or vehicle injection. The kynurenine, serotonin and tryptophan levels were evaluated in the hippocampus by HPLC. Finally, inflammatory and neuroplasticity markers were evaluated in this structure.
Male mice, all the experimental groups showed a higher innate anxiety and anhedonia, with no changes in conflict-based anxiety or behavioral despair. Female mice administered with HFD and LPS displayed anhedonia, while the combination potentiated this effect. No effect on any group was observed in anxiety and behavioral despair.
The combination of HFD and LPS increased inflammatory markers as the kynurenine/tryptophan ratio and STAT-3 in the hippocampus of both male and female mice, while the mTOR pathway was only activated in male mice.
These findings suggest that the double-hit model induces sex-specific differences in the MDD’s behavioral, neurochemical and molecular manifestations.
C57BL/6 male and female mice were fed with normal chow or a High Fat Diet (HFD) for 5 weeks, followed by the acute administration of lipopolysaccharide (LPS): control, HFD, LPS and HFD+LPS groups. Behavioral tests were conducted to evaluate anxious- and depressive-like behaviors after the LPS or vehicle injection. The kynurenine, serotonin and tryptophan levels were evaluated in the hippocampus by HPLC. Finally, inflammatory and neuroplasticity markers were evaluated in this structure.
Male mice, all the experimental groups showed a higher innate anxiety and anhedonia, with no changes in conflict-based anxiety or behavioral despair. Female mice administered with HFD and LPS displayed anhedonia, while the combination potentiated this effect. No effect on any group was observed in anxiety and behavioral despair.
The combination of HFD and LPS increased inflammatory markers as the kynurenine/tryptophan ratio and STAT-3 in the hippocampus of both male and female mice, while the mTOR pathway was only activated in male mice.
These findings suggest that the double-hit model induces sex-specific differences in the MDD’s behavioral, neurochemical and molecular manifestations.
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