title: Transgenic mice overexpressing nesfatin/nucleobindin-2 are susceptible to high-fat diet-induced obesity.
abstract: BACKGROUND
  Nesfatin/Nucleobindin-2 (Nesf/NUCB2), a precursor of nesfatin-1, an anorexigenic protein, is ubiquitously expressed in peripheral tissues in addition to the hypothalamus. However, the role of intracellular Nesf/NUCB2 has not been established in the periphery.
  
  
  METHODS
  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.
  
  
  RESULTS
  No differences were observed in daily food intake and body weight between Nesf/NUCB2-Tg mice (n=11) and their non-Tg littermates (n=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 (n=6) showed significantly higher increase in body weight than their non-Tg littermates fed the same diet (n=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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Diabetes and Endocrinology, International University of Health and Welfare (IUHW) Hospital, Nasushiobara, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Center for Medical Science, IUHW, Otawara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Osaki
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D002149:Energy Intake; D005260:Female; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D000080866:Nucleobindins; D009765:Obesity / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone