Knockdown of leptin A expression dramatically alters zebrafish development

Liu, Qin; Dalman, Mark; Chen, Yun; Akhter, Mashal; Brahmandam, S.; Patel, Yesha; Lowe, Josef; Thakkar, Mitesh; Gregory, Akil-Vuai; Phelps, Daryllanae; Riley, Caitlin; Londraville, Richard L.

doi:10.1016/j.ygcen.2012.07.011

Cited by 36 publications

(47 citation statements)

References 59 publications

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“…Importantly, lepr (leptin receptor) RNA is detected in MG-derived progenitors (Figures 5B and S7A) and Leptin receptor knockdown using a previously verified lepr -targeting MO (Liu et al, 2012), decreased progenitor formation and suppressed the injury-dependent induction of reprogramming genes (Figures 5C–5E). Surprisingly, the effects of Gp130 and Leptin receptor knockdown were not additive (Figures S7B–S7D) and this was also reflected in Stat3-GFP expression (Figures S7E and S7F).…”

Section: Resultsmentioning

confidence: 87%

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Leptin and IL-6 Family Cytokines Synergize to Stimulate Müller Glia Reprogramming and Retina Regeneration

et al. 2014

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Summary Unlike mammals, zebrafish can regenerate a damaged retina. This remarkable regenerative response is mediated by Müller glia (MG) that undergo a reprogramming event that drives their proliferation and the generation of multipotent progenitors for retinal repair. The mechanisms driving MG reprogramming are poorly understood. Here we report that Leptin and Gp130-coupled receptors, acting via a Jak/Stat signaling pathway, stimulate MG reprogramming and progenitor formation in the injured retina. Importantly, we found that ascl1a gene expression, which drives MG reprogramming in fish and mammals, is regulated in a Jak/Stat-dependent manner and requires consensus Stat binding sites for injury-dependent activation. Finally, we identified cytokines that are induced by retinal injury and exhibit a remarkable synergy in their ability to activate Jak/Stat signaling and MG reprogramming in the uninjured retina. Our study not only furthers our understanding of retina regeneration in zebrafish, but also suggests new strategies for awakening retina regeneration in mammals.

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Section: Resultsmentioning

confidence: 87%

“…MO delivery to cells was accomplished by electroporation as previously described (Fausett et al, 2008). The control, ascl1a MO and lepr MO (5’-TGAAGACAGACATCATTTCACTTGC-3’) have been previously described (Fausett et al, 2008; Liu et al, 2012). The gp130 MO is: 5'-ACAGCCAATGATGTGAAGTGTCCAT-3'.…”

Section: Methodsmentioning

confidence: 99%

Leptin and IL-6 Family Cytokines Synergize to Stimulate Müller Glia Reprogramming and Retina Regeneration

et al. 2014

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“…There is evidence that leptin impacts development in many vertebrate species including zebrafish (Liu et al , 2012), frogs (Crespi and Denver, 2006), rodents (Ahima et al , 1999; Erkonen et al , 2011; Hassink et al , 1997; Udagawa et al , 2006), sheep (Ehrhardt et al , 2001; Thomas et al , 2001), and primates (Castracane et al , 2005; Henson et al , 1999). The majority of studies on leptin during pregnancy use rodent models, particularly rats and mice.…”

Section: Leptin’s Role In Pregnancymentioning

confidence: 99%

The impact of leptin on perinatal development and psychopathology

Valleau

Sullivan

2014

Journal of Chemical Neuroanatomy

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Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin’s role and profile during development is examined in available human studies and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where both high and low leptin levels have been correlated with symptomatology. Schizophrenia is also associated with both low and high leptin levels. However, as antipsychotics pharmacotherapy induces weight gain, which elevates leptin levels, drug-naïve populations are needed for further studies. Elevated circulating leptin is consistently found in childhood neurodevelopmental disorders including Autism Spectrum Disorders and Rhett disorder. Further studies on the impact of leptin and leptin resistance on psychopathology and neurodevelopmental disorders are important directions for future research. Studies examining the mechanisms by which exposure to maternal obesity and hyperleptinemia during fetal development impact brain development and behavior are critical for the health of future generations.

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“…Although the tissue distribution pattern of A and B are discrete (suggesting functional differences, (Angotzi et al, 2013; Gorissen et al, 2009), a great majority of fish studies exclusively focus on leptin A (Dalman et al, 2013; Frøiland et al, 2010; Huising et al, 2006; Liu et al, 2012). To date, functional study of leptin B has been limited to expression studies (responds to food restriction- Gorissen et al, 2009; increases during early development- Angotzi et al, 2013), and all manipulations using species-specific recombinant leptins have used leptin A (Dalman et al, 2013; Liu et al, 2012; Lu et al, 2012; Murashita et al, 2011, 2008). …”

Section: Basal Vertebrates Express Multiple Leptin Orthologsmentioning

confidence: 99%

Comparative endocrinology of leptin: Assessing function in a phylogenetic context

Londraville

Macotela

Duff

et al. 2014

General and Comparative Endocrinology

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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.

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Knockdown of leptin A expression dramatically alters zebrafish development

Cited by 36 publications

References 59 publications

Leptin and IL-6 Family Cytokines Synergize to Stimulate Müller Glia Reprogramming and Retina Regeneration

Leptin and IL-6 Family Cytokines Synergize to Stimulate Müller Glia Reprogramming and Retina Regeneration

The impact of leptin on perinatal development and psychopathology

Comparative endocrinology of leptin: Assessing function in a phylogenetic context

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