Leptin deficiency enhances sensitivity to endotoxin-induced lethality
Abstract
Leptin is induced by lipopolysaccharide (LPS) and cytokines. We investigated the role of leptin in LPS-induced toxicity using leptin-deficient ( ob/ ob) and leptin receptor-deficient ( db/ db) mice. Sensitivity to LPS-induced mortality is significantly greater in ob/ obmice compared with their own lean littermates but not in db/ dbmice. LPS reduced serum glucose in both ob/ oband db/ dbmice but induced corticosterone only in db/ dbmice. Despite the very high basal levels of serum leptin in db/ dbmice, a twofold increase in serum leptin levels was observed after LPS in both db/ dbmice and their lean littermates. No differences were detected in LPS-induced serum levels of interleukin (IL)-1β, tumor necrosis factor, macrophage inflammatory protein-1α, and interferon-γ in ob/ obmice compared with their own littermates. In contrast, a blunted induction of IL-10 and IL-1 receptor antagonist (IL-1Ra) was observed in ob/ obmice compared with their littermates. In vitro, leptin induced IL-1Ra production and upregulated the IL-1Ra induction by LPS in macrophages. Moreover, treatment with leptin reversed the increased sensitivity to LPS-induced lethality found in ob/ obmice. These results suggest that leptin participates in the host response to inflammation by modulating the host immune and cytokine responses after LPS.
Key Biomarkers
Symptom Clusters
Cited By (12)
- COVID-19 Severity in Obesity: Leptin and Inflammatory Cytokine Interplay in the Link Between High Morbidity and MortalityFrontiers in Immunology · 2021
- Effect of Maternal Smoking on Breast Milk Interleukin-1α, β-Endorphin, and Leptin ConcentrationsEnvironmental Health Perspectives · 2005
- Endotoxin stimulates leptin in the human and nonhuman primateThe Journal of Clinical Endocrinology & Metabolism · 2003
- Lipopolysaccharide-induced leptin synthesis and release are differentially controlled by alpha-melanocyte-stimulating hormoneNeuroImmunoModulation · 2005
- Leptin modulates gene expression in the heart, cardiomyocytes and the adipose tissue thus mitigating LPS-induced damageExperimental Cell Research · 2021
- Relevance and consequence of chronic inflammation for obesity developmentMolecular and Cellular Pediatrics · 2023
- Invited review: Mechanisms of hypophagia during disease
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