Lipopolysaccharide-Induced Leptin Synthesis and Release Are Differentially Controlled by Alpha-Melanocyte-Stimulating Hormone

Abstract

Objective: Since α-melanocyte-stimulating hormone (α-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 α-MSH increases leptin synthesis and release. Methods: α-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 Thereafter, repeated blood samples were withdrawn over a period of 6 h and plasma leptin concentrations determined.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. α-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 α-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 α-MSH + LPS. LPS increased leptin mRNA by 3-fold at 6 h, whereas it was unaffected in the MSH-treated animals. On the contrary, α-MSH completely blocked the LPS-induced leptin mRNA. Conclusions: Our results suggest that α-MSH increased leptin release without altering its synthesis, but when LPS increased release and synthesis of leptin, α-MSH, although further increasing release, blocked the enhanced synthesis of leptin elicited by LPS.

C-Reactive Protein Increases BBB Permeability: Implications for Obesity and Neuroinflammation

“…Lipopolysaccharide (LPS) can rapidly increase blood leptin concentration [31, 32]. As an acute phase protein, CRP might be a mediator of the effect of LPS on hyperleptinemia.…”

Leptin resistance and desensitization of hypophagia during prolonged inflammatory challenge

“…Two or six hours after the last injection, animals were euthanized by decapitation, blood was collected in ice-cold tubes, and plasma was stored (Ϫ 20°C) for leptin measurements. The time of blood sample collection was based on a previous report showing that plasma leptin response after LPS stimulus is observed between 30 and 360 min (37). Plasma leptin levels were measured by commercial kits (Linco Research, St. Charles, MO).…”

Metabolic syndrome is a low-grade systemic inflammatory condition

“…On the other hand, leptin has proinflammatory actions [44,50], although under certain circumstances it can also be anti-inflammatory in nature. For instance, a-melanocyte-stimulating hormone (a-MSH) that inhibits the synthesis and release of proinflammatory cytokines and stimulates the synthesis and release of anti-inflammatory cytokines has been shown to enhance leptin synthesis and release [51]. Lipopolysaccharide (LPS) enhanced the synthesis and release of leptin that was blocked by a-MSH treatment, suggesting that the pro-and anti-inflammatory actions of leptin might depend on the dose used, the circumstances under investigation and the presence and absence of other molecules.…”