Lipopolysaccharide-induced leptin synthesis and release are differentially controlled by alpha-melanocyte-stimulating hormone.

OBJECTIVE

Since alpha-melanocyte-stimulating hormone (alpha-MSH) inhibits the synthesis and release of proinflammatory cytokines and stimulates the synthesis and release of anti-inflammatory cytokines, and leptin is a cytokine that has anti-inflammatory actions in the presence of lipopolysaccharide (LPS), we hypothesized that alpha-MSH increases leptin synthesis and release.

METHODS

alpha-MSH or 0.9% NaCl (saline) were injected intraperitoneally 15 min prior to intravenous injection of 0.5 ml of saline or LPS (0.15 mg/kg). Thereafter, repeated blood samples were withdrawn over a period of 6 h and plasma leptin concentrations determined. The rats were sacrificed at 6 h and leptin mRNA was measured in epididymal fat pads.

RESULTS

Plasma leptin concentrations of the saline-injected control group were unaltered during the 6 h, whereas in the LPS group, leptin was unaltered between 0 and 30 min and thereafter progressively increased between 30 and 360 min by 2.5-fold. alpha-MSH slightly increased plasma leptin concentrations by 15 min and then increased them further by 120 min, after which they declined towards baseline. The pattern of plasma leptin concentrations in the alpha-MSH + LPS group was similar to that of the LPS group, except that higher concentrations were observed at 120 min in the rats injected with alpha-MSH + LPS. LPS increased leptin mRNA by 3-fold at 6 h, whereas it was unaffected in the MSH-treated animals. On the contrary, alpha-MSH completely blocked the LPS-induced leptin mRNA.

CONCLUSIONS

Our results suggest that alpha-MSH increased leptin release without altering its synthesis, but when LPS increased release and synthesis of leptin, alpha-MSH, although further increasing release, blocked the enhanced synthesis of leptin elicited by LPS.