title: The role of small proliferative adipocytes in the development of obesity: comparison between Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-obese Long-Evans Tokushima Otsuka (LETO) rats.
abstract: Obesity consists of hypertrophy and hyperplasia of adipocytes. Although the number of adipocytes is influenced by anatomical location, nutritional environment, hormone and genetic variation, it has been thought to be determined by the proliferation of precursor cells and subsequent differentiation. However, our recent research has identified the population of small adipocytes less than 20 μm in diameter, exhibiting tiny or no lipid droplets and expressing adipocyte marker proteins (small proliferative adipocytes: SPA) in isolated adipocytes. Notably, 5-bromo-2'-deoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression were detected in these cells. In this study, we investigated the role of SPA in development of adipose tissue using genetically obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and their non-obese and non-diabetic littermates, Long-Evans Tokushima Otsuka (LETO) rats. Proliferation of SPA was determined by measurement of PCNA at the protein level in isolated fractions of adipocytes with collagenase digestion. In general, expression levels of PCNA rose, reached a maximum, and declined in adipose tissues during aging. The expression levels of PCNA were maximum in epididymal fat at 32 w and 12 w of age in LETO and OLETF, respectively. They reached the maximum at 20 w of age both in LETO and OLETF in mesenteric fat. Although the PCNA expression level was higher in OLETF in the early period, it reversed later. Enlargement of adipocytes developed during aging, which was enhanced when the expression levels of PCNA declined. These results suggest that proliferation of SPA may prevent adipocyte hypertrophy and the resultant development of metabolic disorders.
authors.affiliation: Department of General Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hanamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kajita
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mori
authors.forename: Takahide
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kei
authors.initials: K
authors.lastname: Fujioka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okada
authors.forename: Taro
authors.initials: T
authors.lastname: Usui
authors.forename: Noriko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kitada
authors.forename: Koichiro
authors.initials: K
authors.lastname: Taguchi
authors.forename: Toshiko
authors.initials: T
authors.lastname: Kajita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ishizuka
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000473:pathology; D000375:Aging; D000818:Animals; D049109:Cell Proliferation; D003924:Diabetes Mellitus, Type 2; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D020334:Rats, Inbred OLETF
chemical_list: D018809:Proliferating Cell Nuclear Antigen