title: Pegylated leptin antagonist with strong orexigenic activity in mice is not effective in chickens.
abstract: 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.
authors.affiliation: The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University, Rehovot 76100, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Gertler
authors.forename: D
authors.initials: D
authors.lastname: Shinder
authors.forename: S
authors.initials: S
authors.lastname: Yosefi
authors.forename: M
authors.initials: M
authors.lastname: Shpilman
authors.forename: C I
authors.initials: CI
authors.lastname: Rosenblum
authors.forename: M
authors.initials: M
authors.lastname: Ruzal
authors.forename: E
authors.initials: E
authors.lastname: Seroussi
authors.forename: M
authors.initials: M
authors.lastname: Friedman-Einat
authors.forename: M
authors.initials: M
authors.lastname: Freidman-Einat
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002645:Chickens; D004435:Eating / Q000187:drug effects; D005223:Fats / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D054411:Receptors, Leptin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005223:Fats; D020738:Leptin; D054411:Receptors, Leptin
keywords: Chicken leptin; Chicken leptin receptor; Energy balance; Leptin antagonist