Anti-leptin receptor antibodies strengthen leptin biofunction in growing chickens.

Antibodies against the extracellular domains of the chicken leptin receptor were used to study the biological function of leptin in growing chickens. Both polyclonal and monoclonal anti-LEPR antibodies were administered intramuscularly to 30-d-old Chinese indigenous Gushi pullets. Both antibody preparations increased feed intake for 6 h after injection and reduced plasma concentrations of glucose, triglycerides, and both high- and low-density lipoproteins. The antibody treatments also upregulated agouti-related peptide and neuropeptide Y in the hypothalamus and downregulated proopiomelanocortin, melanocortin 4 receptor, and leptin receptor. The treatments also upregulated leptin receptor, acetyl CoA carboxylase beta, and acyl-CoA oxidase in the liver, abdominal fat, and breast muscle and downregulated sterol regulatory element-binding protein-1 and fatty acid synthase. Furthermore, even though the anti-leptin receptor antibodies failed to affect leptin receptor signaling transduction when administered alone, they did augment the induction of leptin receptor signaling transduction by leptin. These results demonstrate that antibodies against the extracellular domains of leptin-specific receptor enhance, but do not mimic, the ability of leptin to activate receptors. Furthermore, the enhanced leptin bioactivity observed after the intramuscular injection of anti-LEPR antibodies confirmed the occurrence of de novo leptin in the peripheral tissues and blood of treated chickens.

Pegylated leptin antagonist with strong orexigenic activity in mice is not effective in chickens.

A chicken gene orthologous to human leptin receptor (LEPR) has been characterized and found to be active in leptin signaling in vitro in response to a variety of recombinant leptins and leptin-containing blood samples. However, the endogenous ligand of chicken LEPR (cLEPR) - the putative chicken leptin - has been reported by us and others to be undetectable at the DNA, mRNA, protein and activity levels. These reports have raised questions as to cLEPR's role. Here we analyzed the effects of a pegylated superactive mouse leptin antagonist (PEG-SMLA) in chicken. We showed that the leptin antagonist efficiently and specifically blocks leptin signaling through the cLEPR in vitro. The effect of the leptin antagonist was then studied in vivo by daily administration of 10 mg kg(-1) for 10 consecutive days to white leghorn female chickens (Gallus gallus) at the age of 2 weeks. Despites the efficient attenuation of the cLEPR in vitro, no effect was observed on body mass, feed intake, feed efficiency or fat accumulation in the treated birds. Because similar treatment in rodents leads to a highly pronounced increase in appetite and body mass that are observed from the first day of treatment, it is concluded that the cLEPR is not implicated in the control of appetite or adipose homeostasis in chickens.