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As we approach the end of two decades of leptin research, the comparative biology of leptin is just beginning. We now have several leptin orthologs described from nearly every major clade among vertebrates, and are moving beyond gene descriptions to functional studies. Even at this early stage, it is clear that non-mammals display clear functional similarities and differences with their better-studied mammalian counterparts. This review assesses what we know about leptin function in mammals and non-mammals, and gives examples of how these data can inform leptin biology in humans., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Using morpholino antisense oligonucleotide (MO) technology, we blocked leptin A or leptin receptor expression in embryonic zebrafish, and analyzed consequences of leptin A knock-down on fish development. Embryos injected with leptin A or leptin receptor MOs (leptin A or leptin receptor morphants) had smaller bodies and eyes, undeveloped inner ear, enlarged pericardial cavity, curved body and/or tail and larger yolk compared to control embryos of the same stages. The defects persisted in 6-9 days old larvae. We found that blocking leptin A function had little effect on the development of early brain (1 day old), but differentiation of both the morphant dorsal brain and retinal cells was severely disrupted in older (2 days old) embryos. Despite the enlarged pericardial cavity, differentiation of cardiac cells appeared to be similar to control embryos. Formation of the morphants' inner ear is also severely disrupted, which corroborates existing reports of leptin receptor expression in inner ear of both zebrafish and mammals. Co-injection of leptin A MO and recombinant leptin results in partial rescue of the wild-type phenotype. Our results suggest that leptin A plays distinct roles in zebrafish development., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Interactions of leptin and leptin receptors play crucial roles during animal development and regulation of appetite and energy balance. In this study we analyzed expression pattern of a zebrafish leptin receptor gene in both developing and adult zebrafish using in situ hybridization and Q-PCR methods. Zebrafish leptin receptor message (lepr) was detected in all embryonic and larval stages examined, and in adult zebrafish. In embryonic zebrafish, lepr was mainly expressed in the notochord. As development proceeded, lepr expression in the notochord decreased, while its expression in several other tissues, including the trunk muscles and gut, became evident. In both larval and adult brains, large lepr expressing cells were detected in similar regions of the hindbrain. In adult zebrafish, lepr expression was also observed in several other brain regions including the hypothalamic lateral tuberal nucleus, the fish homolog of the arcuate nucleus. Q-PCR experiments confirmed lepr expression in the adult fish brain, and also showed lepr expression in several adult tissues including liver, muscle and gonads. Our results showed that lepr expression was both spatially and temporally regulated., ((c) 2009 Elsevier Inc. All rights reserved.)

Green sunfish (Lepomis cyanellus) were injected daily with either murine leptin, phosphate-buffered saline (PBS), or simply handled without injection for 14 days. At the end of the experiment, fish were assayed for intracellular indicators of fatty acid metabolism. Intracellular fatty acid-binding protein (FABP) expression in heart ventricle was twofold higher in the leptin treated group (87.2+/-5.6 Leptin; 47.2+/-6.8 PBS; 28.9+/-3.9 Handled; percent relative expression, Prob.>F<0.001). Two other indicators of intracellular fat metabolism, carnitine palmitoyl transferase activity (CPT) in liver and 3-hydroxyacyl-CoA dehydrogenase (HOAD) in heart were not significantly different among groups, although the trend is for higher values in the leptin treatment (CPT: 0.23+/-0.04 Leptin, 0.11+/-0.04 PBS, 0.10+/-0.03 Handled; U/gm wet weight; Prob.>F=0.08; HOAD: 1.34+/-0.28 Leptin, 0.76+/-0.12 PBS, 0.86+/-0.25 Handled; U/gm wet weight; Prob.>F=0.18). Percent change in total weight, body fat (as a percent of dry weight), cardiosomatic index, and hepatosomatic index were not significantly different among treatments. These results suggest that fish respond to murine leptin injections by increasing fat metabolism, however many of the hallmarks of leptin treatment in mammals (loss of total weight and body fat) were not observed. This lack of response may be due to incompatibility of mouse leptin with fish receptors or an inadequate dose of leptin. We also suggest that leptin's action may be slower in ectotherms due to their lower metabolic rate.

Cadherins are homophilic cell adhesion molecules that control development of a variety of tissues and maintenance of adult structures. In this study, we examined expression of zebrafish cadherin-2 (Cdh2, N-cadherin) and cadherin-4 (Cdh4, R-cadherin) in the visual system of adult zebrafish after eye or optic nerve lesions using immunocytochemistry and immunoblotting. Both Cdh2 and Cdh4 immunoreactivities were specifically up-regulated in regenerating retina and/or the optic pathway. Furthermore, temporal expression patterns of these two cadherins were distinct during the regeneration of the injured tissues. Cadherins have been shown to regulate axonal outgrowth in the developing nervous system, but this is the first report, to our knowledge, of increased cadherin expression associated with axonal regeneration in the vertebrate central nervous system. Our results suggest that both Cdh2 and Cdh4 may be important for regeneration of injured retinal ganglion cell axons.