Ancient Origins and Evolutionary Conservation of Intracellular and Neural Signaling Pathways Engaged by the Leptin Receptor
| Autor: | Rose H. Slupski, Chris Pelletier, Choi Li, Caroline K. Hu, Adam Dziuba, Robert J. Denver, Melissa Y. Cui |
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| Rok vydání: | 2014 |
| Předmět: |
Leptin
medicine.medical_specialty Pituitary gland Molecular Sequence Data Biology Evolution Molecular Mice Xenopus laevis Endocrinology Anterior pituitary Internal medicine Chlorocebus aethiops Neural Pathways medicine Animals Amino Acid Sequence Leptin receptor Sequence Homology Amino Acid Appetite Regulation Suprachiasmatic nucleus digestive oral and skin physiology Pars intermedia Preoptic area medicine.anatomical_structure Hypothalamus COS Cells Receptors Leptin hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Endocrinology. 155:4202-4214 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2014-1301 |
| Popis: | In mammals, leptin acts on leptin receptor (LepR) -expressing neurons in the brain to suppress food intake and stimulate whole-body metabolism. A similar action of leptin on food intake has been reported in the frog Xenopus laevis and in several bony fishes. However, the intracellular signaling and neural pathways by which leptin regulates energy balance have not been investigated outside of mammals. Using reporter assays and site-directed mutagenesis we show that the frog LepR signals via signal transducer and activator of transcription (STAT) 3 and STAT5 through evolutionarily conserved tyrosine residues in the LepR cytoplasmic domain. In situ hybridization histochemistry for LepR mRNA in brain and pituitary showed strong expression in the magno- and parvocellular divisions of the anterior preoptic area (homologous to the mammalian paraventricular nucleus), the suprachiasmatic nucleus, ventral hypothalamus, and pars intermedia and pars distalis of the anterior pituitary. Leptin injection increased phosphorylated STAT3 immunoreactivity in LepR mRNA-positive cells, and induced socs3 and pomc mRNAs. Microarray analysis of preoptic area/hypothalamus/pituitary 2 hours after leptin injection identified leptin-regulated genes that included c-fos, a known leptin-activated gene; pituitary follicle-stimulating hormone subunit β, suggesting an important role for leptin in the reproductive axis of frogs; and B-cell translocation factor 2, which has important functions in neurogenesis. Our findings support that the intracellular signaling pathways and neural substrates that mediate leptin actions on energy balance were present in the common ancestor of modern amphibians and amniotes and have been conserved over 350 million years of evolutionary time. |
| Databáze: | OpenAIRE |
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