title: Possible involvement of hypothalamic nucleobindin-2 in hyperphagic feeding in Tsumura Suzuki obese diabetes mice.
abstract: The aim of this study was to clarify the hypothalamic neuropeptides that are associated with hyperphagic feeding in Tsumura Suzuki Obese Diabetes (TSOD) mice, a model of type 2 diabetes with polygenic abnormalities. TSOD mice showed an increase in body weight and hyperleptinemia from 1 month of age and hyperphagic feeding, hyperglycemia, hyperlipidemia and hyperinsulinemia from 3 to 12 months of age compared with age-matched non-diabetic control Tsumura Suzuki Non Obesity (TSNO) mice. The mRNA level of nucleobindin-2 (NUCB2), the precursor of the anorexigenic neuropeptide nesfatin-1, was significantly decreased in the hypothalamus of TSOD mice compared with that in TSNO mice from 3 to 12 months of age. The protein level of NUCB2 was significantly decreased in the hypothalamus of TSOD mice compared with that in TSNO mice at 3 months of age. The mRNA levels of galanin, melanin-concentrating hormone, neuropeptide Y, and pro-opiomelanocortin were significantly changed in the hypothalamus in TSOD mice at several time points. Another model of type 2 diabetes, db/db mice, which is a mutant mouse that lacks a functional leptin receptor, showed hyperphagic feeding but no change in hypothalamic NUCB2 mRNA compared with non-diabetic control db/+ mice. The results suggest that the disrupted control of hypothalamic NUCB2-mediated signaling may contribute to hyperphagic feeding in TSOD mice. In addition, the mechanism for the development of hyperphagic feeding in TSOD mice is different than that in db/db mice.
authors.affiliation: Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1–1–20 Shin-machi, Nishitokyo, Tokyo 202–8585, Japan. s_miyata@gunma-u.ac.jp
authors.forename: Shigeo
authors.initials: S
authors.lastname: Miyata
authors.forename: Nao
authors.initials: N
authors.lastname: Yamada
authors.forename: Tomie
authors.initials: T
authors.lastname: Kawada
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006963:Hyperphagia / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000080866:Nucleobindins; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D012333:RNA, Messenger