A Role of Central NELL2 in the Regulation of Feeding Behavior in Rats

Jeong, Jin Kwon; Kim, Jae Geun; Kim, Han Rae; Lee, Tae Hwan; Park, Jeong Woo; Lee, Byung Ju

doi:10.14348/molcells.2017.2278

Cited by 12 publications

(14 citation statements)

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“…investigated NELL2‐regulated feeding behavior. A block of NELL2 production led to a decrease in daily food intake followed by a loss in body weight (Jeong et al., 2017). According to the parents’ report, our patient showed feeding difficulties in the first 3 months.…”

Section: Discussionmentioning

confidence: 99%

Deletion at 12q12 increases the risk of developmental delay and intellectual disability

Weng

Luo

Hou

2018

Annals of Human Genetics

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Single‐nucleotide polymorphism (SNP) arrays have been widely used to identify novel genomic imbalances. Many of these genomic imbalances have been confirmed to interact with developmental delays, intellectual disabilities (IDs), and congenital defects. Here, we identify a Chinese girl with a 3.18‐Mb deletion at 12q12 (human genome build 19: 43,418,911‐46,601,627) who showed postnatal growth delay, low‐set ears, small hands and feet, widely spaced nipples, and blue sclerae. Deletions at 12q12 are extremely rare chromosomal imbalances; only four cases involving a deletion of this type have previously been reported. In these five sporadic cases, all of the patients exhibited developmental issues accompanied by different degrees of ID. A review of DECIPHER patient data revealed an additional six cases involving genomic deletion at 12q12. Many of the patients in these cases exhibited developmental delay and ID. When these patients were included, 91% and 73% of individuals with a deletion in this chromosomal region presented with developmental retardation and ID, respectively. Database searches indicated that this copy number variant (CNV) has not been found in normal humans. Therefore, we suggest that a CNV in this region is a risk factor for developmental retardation and ID.

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Section: Discussionmentioning

confidence: 99%

Deletion at 12q12 increases the risk of developmental delay and intellectual disability

Weng

Luo

Hou

2018

Annals of Human Genetics

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“…We also observed in this study that mRNA level of NELL2 expression in the hypothalamus was elevated during fasting, when compared to a fed state. Therefore, it is likely that central NELL2 is responsible for an orexigenic mechanism in rodents.Anatomical verification revealed that NELL2 is produced both in neuropeptide Y (NPY) and proopiomelanocortin (POMC) cells in the ARC, both of which are critical in metabolism regulation through functional opposition [7]. Therefore, we also investigated whether NELL2 signaling is associated with gene expression of NPY and POMC.…”

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confidence: 99%

“…Although NELL2 is broadly distributed throughout the mammalian brain, we previously reported that its expression is brain region-specific and cell type-dependent [5]. Importantly, NELL2 is produced relatively high in the hypothalamus compared to other brain regions [5,7]. In addition, core hypothalamic nuclei known to play a critical role in metabolism regulation, such as the paraventricular nucleus, ventromedial nucleus, and the arcuate nucleus of the hypothalamus (ARC) are also a main site of NELL2 production [5,7].…”

mentioning

confidence: 99%

“…Importantly, NELL2 is produced relatively high in the hypothalamus compared to other brain regions [5,7]. In addition, core hypothalamic nuclei known to play a critical role in metabolism regulation, such as the paraventricular nucleus, ventromedial nucleus, and the arcuate nucleus of the hypothalamus (ARC) are also a main site of NELL2 production [5,7]. This anatomical observation allowed us to hypothesize a potential function of NELL2 in whole body metabolism regulation.Recently, we reported "A Role of Central NELL2 in the Regulation of Feeding Behavior in Rats" [7].…”

mentioning

confidence: 99%

“…In addition, core hypothalamic nuclei known to play a critical role in metabolism regulation, such as the paraventricular nucleus, ventromedial nucleus, and the arcuate nucleus of the hypothalamus (ARC) are also a main site of NELL2 production [5,7]. This anatomical observation allowed us to hypothesize a potential function of NELL2 in whole body metabolism regulation.Recently, we reported "A Role of Central NELL2 in the Regulation of Feeding Behavior in Rats" [7]. In this work, we demonstrated a role for central NELL2 in rodent feeding behavior and energy homeostasis, using an antisense oligonucleotide-dependent gene blocking system for an acute ablation of NELL2 biosynthesis in adult rodent brain in vivo.…”

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confidence: 99%

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Versatile role of NELL2 in brain

Kim¹,

Jeong²

2018

J Cell Signal

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CommentaryA precise communication between the central nervous system (CNS) and the periphery is fundamental in achieving a fine balance between energy intake and expenditure. When this crosstalk is impaired, obesity, a metabolic state characterized by excess fat accumulation in peripheral tissues, occurs. Obesity is the foundation for several metabolic syndromes, such as type 2 diabetes, stroke, and hypertension, all of which are leading causes of mortality. It is no doubt that multiple regions of the brain participate in the regulation of energy homeostasis. However, the hypothalamus has long been highlighted in metabolism regulation as it forms a coherent whole for direct detection of circulating metabolic signals, integration of metabolic information obtained from periphery and other CNS regions, and production of adequate molecular and behavioral outcomes that preserve whole body energy homeostasis [1][2][3][4].NELL2, a mammalian neural tissue-enriched EGF-Like Like protein 2, is a newly identified secreting molecule from neurons as a neurotransmitter [5,6]. Although NELL2 is broadly distributed throughout the mammalian brain, we previously reported that its expression is brain region-specific and cell type-dependent [5]. Importantly, NELL2 is produced relatively high in the hypothalamus compared to other brain regions [5,7]. In addition, core hypothalamic nuclei known to play a critical role in metabolism regulation, such as the paraventricular nucleus, ventromedial nucleus, and the arcuate nucleus of the hypothalamus (ARC) are also a main site of NELL2 production [5,7]. This anatomical observation allowed us to hypothesize a potential function of NELL2 in whole body metabolism regulation.Recently, we reported "A Role of Central NELL2 in the Regulation of Feeding Behavior in Rats" [7]. In this work, we demonstrated a role for central NELL2 in rodent feeding behavior and energy homeostasis, using an antisense oligonucleotide-dependent gene blocking system for an acute ablation of NELL2 biosynthesis in adult rodent brain in vivo. Importantly, adult rats with acute hypothalamic NELL2 ablation showed a significant reduction in body weight gain under ad libitum, normal chow feeding conditions when compared to controls. This response was attributed to a reduction in food intake behavior. On the other hand, blockade of NELL2 in the hypothalamus did not affect animal's water intake, nor produced sickness behavior. These behavioral studies have demonstrated a role of hypothalamic NELL2 signaling in feeding behavior. Interestingly, short-term food intake followed by overnight fasting was not differ between experimental and control groups, suggesting that NELL2 signaling in the hypothalamus is specific for ad libitum appetite behavior. We also observed in this study that mRNA level of NELL2 expression in the hypothalamus was elevated during fasting, when compared to a fed state. Therefore, it is likely that central NELL2 is responsible for an orexigenic mechanism in rodents.Anatomical verification revealed that NELL2 i...

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