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

Gertler, Arieh; Shinder, D.; Yosefi, Sara; Shpilman, Michal; Rosenblum, Charles; Ruzal, M.; Seroussi, Eyal; Friedman-Einat, Miriam

doi:10.1242/jeb.095539

Cited by 10 publications

(5 citation statements)

References 46 publications

(95 reference statements)

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“…The leptin gene was not identifiable in the latter, however we were able to download and assemble the matching SRA sequence reads (Figure 2), which correspond to an intact exon 3 structure. We repeated the sequence searches against the chicken genome and confirmed that even this galliforme LEP -like sequence is not detectable in Gallus gallus , in agreement with the observation that administration of a leptin antagonist had no effect on appetite and body growth of layer chickens [31]. We could not associate any ESTs or RNA-seq reads to the quails’ leptin-like genes and moreover the role of the leptin signaling pathway may differ in galliformes [28].…”

Section: Resultssupporting

confidence: 69%

Quack leptin

Friedman-Einat

Seroussi

2014

BMC Genomics

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BackgroundA LEP transcript up-regulated in lungs of ducks (Anas platyrhynchos) infected by avian influenza A virus was recently described in the Nature Genetics manuscript that reported the duck genome. In vertebrates, LEP gene symbol is reserved for leptin, the key regulator of energy balance in mammals.ResultsLaunching an extensive search for this gene in the genome data that was submitted to the public databases along with duck genome manuscript and extending this search to all avian genomes in the whole-genome shotgun-sequencing database, we were able to report the first identification of coding sequences capable of encoding the full leptin protein precursor in wild birds. Gene structure, synteny and sequence-similarity (up to 54% identity and 68% similarity) to reptilian leptin evident in falcons (Falco peregrinus and cherrug), tits (Pseudopodoces humilis), finches (Taeniopygia guttata) and doves (Columba livia) confirmed that the bird leptin was a true ortholog of its mammalian form. Nevertheless, in duck, like other domestic fowls the LEP gene was not identifiable.ConclusionLack of the LEP gene in poultry suggests that birds that have lost it are particularly suited to domestication. Identification of an intact avian gene for leptin in wild birds might explain in part the evolutionary conservation of its receptor in leptin-less fowls.

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Section: Resultssupporting

confidence: 69%

Quack leptin

Friedman-Einat

Seroussi

2014

BMC Genomics

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“…However, the existence of functional LEP genes in chickens, Japanese quail and the mallard duck has yet to be proven . suggest that this may be associated with changes in appetite regulation linked to domestication, and that it is in line with the observation that a pegylated leptin antagonist that inhibited activation of a LEPR bioassay reporter system by rock dove leptin was ineffective in altering food intake and body mass in chickens (Gertler et al, 2014). However, that conclusion is dependent on LEP having a physiological role in energy balance regulation in the chicken, which may not be the case.…”

Section: Regulation Of Agrp and Pomc Gene Expression By Leptinsupporting

confidence: 65%

Regulation of the avian central melanocortin system and the role of leptin

Boswell

Dunn

2015

General and Comparative Endocrinology

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The avian central melanocortin system is well conserved between birds and mammals in terms of the component genes, the localisation of their expression in the hypothalamic arcuate nucleus, the effects on feeding behaviour of their encoded peptides and the sensitivity of agouti-related protein (AGRP) and pro-opiomelanocortin (POMC) gene expression to changes in energy status. Our recent research has demonstrated that AGRP gene expression precisely differentiates between broiler breeder hens with different histories of chronic food restriction and refeeding. We have also shown that the sensitivity of AGRP gene expression to loss of energy stores is maintained even when food intake has been voluntarily reduced in chickens during incubation and in response to a stressor. However, the similarity between birds and mammals does not appear to extend to the way AGRP and POMC gene expression are regulated. In particular, the preliminary evidence from the discovery of the first avian leptin (LEP) genes suggests that LEP is more pleiotropic in birds and may not even be involved in regulating energy balance. Similarly, ghrelin exerts inhibitory, rather than stimulatory, effects on food intake. The fact that the importance of these prominent long-term regulators of AGRP and POMC expression in mammals appears diminished in birds suggests that the balance of regulatory inputs in birds may have shifted to more short-term influences such as the tone of cholecystokinin (CCK) signalling. This is likely to be related to the different metabolic fuelling required to support flight.

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“…Interestingly, we noted that avian leptin mRNA is predominantly expressed in the brain and pituitary, but undetectable in peripheral tissues including adipose tissue [ 63 ]. This finding, together with little effect of icv injection of leptin on food intake of chickens [ 68 , 69 ], also points to a possibility that unlike that in mammals, metabolic signal(s) other than leptin associated with negative energy balance from peripheral tissues may control c CART1 mRNA expression in chicken hypothalamus ( Fig 6 ).…”

Section: Discussionmentioning

confidence: 97%

Characterization of the Two CART Genes (CART1 and CART2) in Chickens (Gallus gallus)

Cai

Huang

et al. 2015

PLoS ONE

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Cocaine- and amphetamine-regulated transcript (CART) peptide is implicated in the control of avian energy balance, however, the structure and expression of CART gene(s) remains largely unknown in birds. Here, we cloned and characterized two CART genes (named cCART1 and cCART2) in chickens. The cloned cCART1 is predicted to generate two bioactive peptides, cCART1(42-89) and cCART1(49-89), which share high amino acid sequence identity (94-98%) with their mammalian counterparts, while the novel cCART2 may produce a bioactive peptide cCART2(51-91) with 59% identity to cCART1. Interestingly, quantitative RT-PCR revealed that cCART1 is predominantly expressed in the anterior pituitary and less abundantly in the hypothalamus. In accordance with this finding, cCART1 peptide was easily detected in the anterior pituitary by Western blot, and its secretion from chick pituitaries incubated in vitro was enhanced by ionomycin and forskolin treatment, indicating that cCART1 is a novel peptide hormone produced by the anterior pituitary. Moreover, cCART1 mRNA expression in both the pituitary and hypothalamus is down-regulated by 48-h fasting, suggesting its expression is affected by energy status. Unlike cCART1, cCART2 is only weakly expressed in most tissues examined by RT-PCR, implying a less significant role of cCART2 in chickens. As in chickens, 2 or more CART genes, likely generated by gene and genome duplication event(s), were also identified in other non-mammalian vertebrate species including coelacanth. Collectively, the identification and characterization of CART genes in birds helps to uncover the roles of CART peptide(s) in vertebrates and provides clues to the evolutionary history of vertebrate CART genes.

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

Cited by 10 publications

References 46 publications

Quack leptin

Quack leptin

Regulation of the avian central melanocortin system and the role of leptin

Characterization of the Two CART Genes (CART1 and CART2) in Chickens (Gallus gallus)

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