title: Necdin controls proliferation of white adipocyte progenitor cells.
abstract: White adipose tissues are composed mainly of white fat cells (adipocytes), which play a key role in energy storage and metabolism. White adipocytes are terminally differentiated postmitotic cells and arise from their progenitor cells (preadipocytes) or mesenchymal stem cells residing in white adipose tissues. Thus, white adipocyte number is most likely controlled by the rate of preadipocyte proliferation, which may contribute to the etiology of obesity. However, little is known about the molecular mechanisms that regulate preadipocyte proliferation during adipose tissue development. Necdin, which is expressed predominantly in postmitotic neurons, is a pleiotropic protein that possesses anti-mitotic and pro-survival activities. Here we show that necdin functions as an intrinsic regulator of white preadipocyte proliferation in developing adipose tissues. Necdin is expressed in early preadipocytes or mesenchymal stem cells residing in the stromal compartment of white adipose tissues in juvenile mice. Lentivirus-mediated knockdown of endogenous necdin expression in vivo in adipose tissues markedly increases fat mass in juvenile mice fed a high-fat diet until adulthood. Furthermore, necdin-null mutant mice exhibit a greater expansion of adipose tissues due to adipocyte hyperplasia than wild-type mice when fed the high-fat diet during the juvenile and adult periods. Adipose stromal-vascular cells prepared from necdin-null mice differentiate in vitro into a significantly larger number of adipocytes in response to adipogenic inducers than those from wild-type mice. These results suggest that necdin prevents excessive preadipocyte proliferation induced by adipogenic stimulation to control white adipocyte number during adipose tissue development.
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
authors.forename: Kazushiro
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Koichi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ohkumo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Tseng
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yoshikawa
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism / Q000502:physiology; D014162:Transfection
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C069766:necdin