Format

Send to

Choose Destination
Am J Pathol. 2000 May;156(5):1781-7.

Reduced leptin levels in starvation increase susceptibility to endotoxic shock.

Author information

1
Metabolism Section, Department of Veterans Affairs Medical Center, University of California, San Francisco, California 94121, USA.

Abstract

Malnutrition compromises immune function, reducing resistance to infection. We examine whether the decrease in leptin induced by starvation increases susceptibility to lipopolysaccharide (LPS)- and tumor necrosis factor (TNF)-induced lethality. In mice, fasting for 48 hours enhances sensitivity to LPS. Decreasing the fasting-induced fall in leptin by leptin administration markedly reduced sensitivity to LPS. Although fasting decreases basal leptin levels, LPS treatment increased leptin to the same extent as in fed animals. Fasting increased basal serum corticosterone; leptin treatment blunted this increase. Fasting decreased the ability of LPS to increase corticosterone; leptin restored the corticosterone response to LPS. Serum glucose levels were decreased in fasted mice and LPS induced a further decrease. Leptin treatment affected neither basal glucose nor that after LPS. LPS induced a fivefold greater increase in serum TNF in fasted mice, which was blunted by leptin replacement. In contrast, LPS induced lower levels of interferon-gamma and no differences in interleukin-1beta in fasted compared to fed animals; leptin had no effect on those cytokines. Furthermore, fasting increased sensitivity to the lethal effect of TNF itself, which was also reversed by leptin treatment. Thus, leptin seems to be protective by both inhibiting TNF induction by LPS and by reducing TNF toxicity.

PMID:
10793089
PMCID:
PMC1876910
DOI:
10.1016/S0002-9440(10)65049-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center