Leptin Gene Expression in the Brain and Pituitary Gland

Morash, Barbara; Li, Audrey; Murphy, Paul R.; Wilkinson, Michael; Ur, Ehud

doi:10.1210/endo.140.12.7288

Cited by 281 publications

(145 citation statements)

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“…44 Several other genes for which placental methylation has been associated with infant health are also expressed in the brain, such as HTR2A, 45 NR3C1, 46 FKBP5, 47 and LEP. 48 Epigenetic regulation by the placenta may influence these important neuropeptides that direct the development and function of the fetal brain. Additionally, it is possible that the DNA methylation patterns in the placenta are indicative of those within the fetal brain, thus making the placenta a surrogate tissue.…”

Section: Discussionmentioning

confidence: 99%

Regions of variable DNA methylation in human placenta associated with newborn neurobehavior

et al. 2016

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(2016) Regions of variable DNA methylation in human placenta associated with newborn neurobehavior, Epigenetics, 11:8, 603-613, DOI: 10.1080/15592294.2016 ABSTRACTThe placenta regulates the in utero environment and functionally impacts fetal development. Candidate gene studies identified variation in placental DNA methylation is associated with newborn neurologic and behavioral outcomes including movement quality, lethargic behavior, attention, and arousal. We sought to identify novel regions of variable DNA methylation associated with newborn attention, lethargy, quality of movement, and arousal by performing an epigenome-wide association study in 335 infants from a US birth cohort. Methylation status was quantified using the Illumina HumanMethylation450 BeadChip array and associations to newborn outcomes assessed by the NICU Network Neurobehavioral Scales (NNNS) were identified while incorporating established bioinformatics algorithms to control for confounding by cell type composition. Methylation of CpGs within FHIT (cg15970800) and ANKRD11 (cg16710656) demonstrated genome-wide significance (P < 1.8 £ 10 ¡7 ) in specific associations with infant attention. CpGs whose differential methylation was associated with all 4 neurobehavioral outcomes were common to 50 genes involved in biological processes relating to cellular adhesion and nervous system development. Comprehensive methylation profiling identified relationships between methylation of FHIT and ANKRD11, which have been previously linked to neurodevelopment and behavioral outcomes in genetic association studies. Subtle changes in DNA methylation of these genes within the placenta may impact normal variation of a newborn's ability to alter and track visual and auditory stimuli. Gene ontology analysis suggested that those genes with variable methylation related to these outcomes are overrepresented in biological pathways involved in brain development and placental physiology, supportive of our hypothesis for a key role of the placenta in neurobehavioral outcomes.

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Section: Discussionmentioning

confidence: 99%

Regions of variable DNA methylation in human placenta associated with newborn neurobehavior

et al. 2016

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“…In hippocampal neurons, the expression of leptin receptors is also reportedly influenced by fasting [8]. Several studies have also demonstrated expression of leptin mRNA and protein throughout the CNS, suggesting that leptin may be released locally from specific neuronal populations [9].…”

Section: Introductionmentioning

confidence: 99%

Leptin regulation of hippocampal synaptic function in health and disease

Irving

Harvey

2014

Phil. Trans. R. Soc. B

102

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The endocrine hormone leptin plays a key role in regulating food intake and body weight via its actions in the hypothalamus. However, leptin receptors are highly expressed in many extra-hypothalamic brain regions and evidence is growing that leptin influences many central processes including cognition. Indeed, recent studies indicate that leptin is a potential cognitive enhancer as it markedly facilitates the cellular events underlying hippocampal-dependent learning and memory, including effects on glutamate receptor trafficking, neuronal morphology and activity-dependent synaptic plasticity. However, the ability of leptin to regulate hippocampal synaptic function markedly declines with age and aberrant leptin function has been linked to neurodegenerative disorders such as Alzheimer's disease (AD). Here, we review the evidence supporting a cognitive enhancing role for the hormone leptin and discuss the therapeutic potential of using leptin-based agents to treat AD.

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“…Nevertheless, recent works indicate that leptin gene is also expressed in placenta (Senaris et al 1997), stomach (Bado et al 1998), heart (Matsui et al 2007), skeletal muscle (Wang et al 1998), and mammary gland (Smith-Kirwin et al 1998). Morash et al (1999) also report that gene and protein of leptin are expressed in rat cortex, cerebellum, hypothalamus, and pituitary gland in the CNS (Morash et al 1999). Either overexpression or lack of leptin can result in phenotypic abnormalities, such as obesity (Hsing et al 2007) or hypertension (Tumer et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Leptin induces migration and invasion of glioma cells through MMP‐13 production

Yeh

Lee

et al. 2008

Glia

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Leptin, the product of the obses gene, plays an important role in the regulation of body weight by coordinating metabolism, feeding behavior, energy balance and neuroendocrine responses. However, central regulation of leptin gene expression is different from that in the adipocytes. In addition, leptin has been found in many tumor cell lines and has been shown to have mitogenic and angiogenic activity in a number of cell types. Glioma is the most common primary adult brain tumor with poor prognosis due to the spreading of tumor cell to the other regions of brain easily. Here we found that malignant C6 glioma cells expressed more leptin and leptin receptors than non-malignant astrocytes. Furthermore, it was found that exogenous application of leptin enhanced the migration and invasion of C6 glioma cells. In addition, we found that the expression of matrix metalloproteinase-13 (MMP-13) but not of MMP-2 and MMP-9 was increased in response to leptin stimulation. The leptin-induced increase of cell migration and invasion was antagonized by MMP-13 neutralizing antibody or silencing MMP-13. The up-regulation of MMP-13 induced by leptin was mainly through p38 MAP kinase and NF-κB pathway. In addition, migration-prone sublines demonstrate that cells with increasing migration ability had more expression of MMP-13 and leptin. Taken together, these results indicate that leptin enhanced migration and invasion of C6 glioma cells through the increase of 2

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Leptin Gene Expression in the Brain and Pituitary Gland

Cited by 281 publications

References 0 publications

Regions of variable DNA methylation in human placenta associated with newborn neurobehavior

Regions of variable DNA methylation in human placenta associated with newborn neurobehavior

Leptin regulation of hippocampal synaptic function in health and disease

Leptin induces migration and invasion of glioma cells through MMP‐13 production

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