A Role of Central NELL2 in the Regulation of Feeding Behavior in Rats
Jin Kwon Jeong1,*, Jae Geun Kim2, Han Rae Kim3, Tae Hwan Lee3, Jeong Woo Park3, and
Byung Ju Lee3,*
1Department of Pharmacology and Physiology, School of Medicine & Health Sciences, The George Washington University, USA, 2Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea, 3Department of Biological Sciences, University of Ulsan, Ulsan 44610, Korea
*Correspondence: jinkwon0911@gwu.edu (JKJ); bjlee@ulsan.ac.kr (BJL)
Received November 6, 2016; Revised February 21, 2017; Accepted March 6, 2017.; Published online March 15, 2017.
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A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored. Metabolic state-dependent NELL2 expression in the hypothalamus was tested in vivo using a fasting model. NELL2 was noticeably expressed in the hypothalamic nuclei controlling feeding behavior. Furthermore, all arcuatic POMC and NPY positive neurons produced NELL2. The NELL2 gene expression in the hypothalamus was up-regulated by fasting. However, NELL2 did not affect POMC and NPY gene expression in the hypothalamus. A blockade of NELL2 production in the hypothalamus led to a reduction in daily food intake, followed by a loss in body weight without a change in daily water intake in normal diet condition. NELL2 did not affect short-term hunger dependent appetite behavior. Our data suggests that hypothalamic NELL2 is associated with appetite behavior, and thus central NELL2 could be a new therapeutic target for obesity.
Keywords: feeding behavior, hypothalamus, metabolic state, NELL2, neural plasticity

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