Avian blood induced intranuclear translocation of STAT3 via the chicken leptin receptor

Ohkubo, Tadayasu; Hirota, Kanako; Murase, Daisuke; Adachi, Hiromi; Nozawa-Takeda, Tsutomu; Sugita, Shoei

doi:10.1016/j.cbpb.2014.05.001

Cited by 10 publications

(4 citation statements)

References 38 publications

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“…Expression vectors containing the chicken leptin receptor cDNA (pCI-chLEPR called hereafter p-ObR), green fluorescent protein (GFP)-fused chicken signal transducer and activator of transcription 3 cDNA (p-STAT3), and both (p-ObR+STAT3) have been described previously (Adachi et al, 2008 ; Ohkubo et al, 2014 ). The backbone vectors pCI-neo and pEGFP-N1 were obtained from Promega (Tokyo, Japan) and were used as controls.…”

Section: Methodsmentioning

confidence: 99%

AMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manner

et al. 2018

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Autophagy, a highly conserved intracellular self-digestion process, plays an integral role in maintaining cellular homeostasis. Although emerging evidence indicate that the endocrine system regulates autophagy in mammals, there is still a scarcity of information on autophagy in avian (non-mammalian) species. Here, we show that intracerebroventricular administration of leptin reduces feed intake, modulates the expression of feeding-related hypothalamic neuropeptides, activates leptin receptor and signal transducer and activator of transcription (Ob-Rb/STAT) pathway, and significantly increases the expression of autophagy-related proteins (Atg3, Atg5, Atg7, beclin1, and LC3B) in chicken hypothalamus, liver, and muscle. Similarly, leptin treatment activates Ob-Rb/STAT pathway and increased the expression of autophagy-related markers in chicken hypothalamic organotypic cultures, muscle (QM7) and hepatocyte (Sim-CEL) cell cultures as well as in Chinese Hamster Ovary (CHO-K1) cells-overexpressing chicken Ob-Rb and STAT3. To define the downstream mediator(s) of leptin's effects on autophagy, we determined the role of the master energy sensor AMP-activated protein kinase (AMPK). Leptin treatment significantly increased the phosphorylated levels of AMPKα1/2 at Thr172 site in chicken hypothalamus and liver, but not in muscle. Likewise, AMPKα1/2 was activated by leptin in chicken hypothalamic organotypic culture and Sim-CEL, but not in QM7 cells. Blocking AMPK activity by compound C reverses the autophagy-inducing effect of leptin. Together, these findings indicate that AMPK mediates the effect of leptin on chicken autophagy in a tissue-specific manner.

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Section: Methodsmentioning

confidence: 99%

AMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manner

et al. 2018

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“…Several lines of evidence support this hypothesis: bird leptin expression is primarily in CNS (42, 45), bird blood did not activate a sensitive chicken leptin receptor assay, even in birds with extreme adiposity (46), and genes with high GC content (such as bird leptin genes) are associated with low transcription rates (47). One study that supported a circulating leptin in birds documented that chicken serum and crow blood caused translocation of GFP-labeled STAT 3 to the nucleus in an expressed chicken leptin receptor assay (48). However, potent leptin receptor antagonists tested in chickens effectively block chicken leptin receptor in vitro but not in vivo (49).…”

Section: Evolution Of Leptin Signaling: Is There Another Major Signalmentioning

confidence: 99%

On the Molecular Evolution of Leptin, Leptin Receptor, and Endospanin

et al. 2017

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Over a decade passed between Friedman’s discovery of the mammalian leptin gene (1) and its cloning in fish (2) and amphibians (3). Since 2005, the concept of gene synteny conservation (vs. gene sequence homology) was instrumental in identifying leptin genes in dozens of species, and we now have leptin genes from all major classes of vertebrates. This database of LEP (leptin), LEPR (leptin receptor), and LEPROT (endospanin) genes has allowed protein structure modeling, stoichiometry predictions, and even functional predictions of leptin function for most vertebrate classes. Here, we apply functional genomics to model hundreds of LEP, LEPR, and LEPROT proteins from both vertebrates and invertebrates. We identify conserved structural motifs in each of the three leptin signaling proteins and demonstrate Drosophila Dome protein’s conservation with vertebrate leptin receptors. We model endospanin structure for the first time and identify endospanin paralogs in invertebrate genomes. Finally, we argue that leptin is not an adipostat in fishes and discuss emerging knockout models in fishes.

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“…Also, although short isoforms of the avian LEPR have been identified (Liu et al, 2007b) the most abundant avian LEPR isoform is orthologous to the mammalian Rb long isoform and none has so far been shown to be equivalent to the mammalian Ra short isoform thought to be involved in the transport of LEP into the brain. Collectively, these data may indicate a more paracrine role for leptin in birds, although rock dove and possibly other avian sera have recently been shown to activate LEPR reporter bioassays Ohkubo et al, 2014).…”

Section: Regulation Of Agrp and Pomc Gene Expression By Leptinmentioning

confidence: 98%

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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Avian blood induced intranuclear translocation of STAT3 via the chicken leptin receptor

Cited by 10 publications

References 38 publications

AMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manner

AMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manner

On the Molecular Evolution of Leptin, Leptin Receptor, and Endospanin

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

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