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However, the role of intracellular Nesf\/NUCB2 has not been established in the periphery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Nesf\/NUCB2-transgenic (Tg) mice were generated, and chronological changes of body weight and daily food intake were measured in Nesf\/NUCB2-Tg mice fed normal laboratory chow or 45% high-fat diet (HFD). In addition, changes of metabolic markers were evaluated in those mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>No differences were observed in daily food intake and body weight between Nesf\/NUCB2-Tg mice (<jats:italic>n<\/jats:italic>=11) and their non-Tg littermates (<jats:italic>n<\/jats:italic>=11) fed normal chow. Nesf\/NUCB2-Tg mice showed increased mRNA expression of oxytocin and corticotropin-releasing hormone and decreased mRNA expression of cocaine- and amphetamine-related transcript in the hypothalamus. Nesf\/NUCB2-Tg mice fed 45% HFD (<jats:italic>n<\/jats:italic>=6) showed significantly higher increase in body weight than their non-Tg littermates fed the same diet (<jats:italic>n<\/jats:italic>=8); however, no difference was observed in daily food intake between these two groups. Further, Nesf\/NUCB2-Tg mice fed 45% HFD showed a significant increase in the weight of the liver, subcutaneous fat, and brown adipose tissue and decrease in the expression of uncoupling protein-1 in the subcutaneous fat. Blood glucose levels of Nesf\/NUCB2-Tg mice fed 45% HFD were not different from those of their non-Tg littermates fed the same diet. Insulin levels of these Tg mice were significantly higher than those of their non-Tg littermates. Histological analysis showed marked fat deposition in the hepatocytes surrounding the hepatic central veins in Nesf\/NUCB2-Tg mice fed 45% HFD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Overexpression of Nesf\/NUCB2 did not change food intake, but increased body weight only in Nesf\/NUCB2-Tg mice fed HFD. The results of this study indicate that Nesf\/NUCB2 was involved in the development of insulin resistance and fat deposition in the liver, independent of the modulation of energy intake.<\/jats:p><\/jats:sec>","DOI":"10.1038\/nutd.2015.42","type":"journal-article","created":{"date-parts":[[2016,3,7]],"date-time":"2016-03-07T15:22:45Z","timestamp":1457364165000},"page":"e201-e201","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Transgenic mice overexpressing nesfatin\/nucleobindin-2 are susceptible to high-fat diet-induced obesity"],"prefix":"10.1038","volume":"6","author":[{"given":"H","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Osaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,7]]},"reference":[{"key":"BFnutd201542_CR1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/nature05162","volume":"443","author":"S Oh-I","year":"2006","unstructured":"Oh-I S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K et al. 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