title: Pioglitazone enhances small-sized adipocyte proliferation in subcutaneous adipose tissue.
abstract: The possibility that mature adipocytes proliferate has not been fully investigated.  In this study, we demonstrate that adipocytes can proliferate.  5-bromo-2'-deoxyuridine (BrdU)-labeled adipocyte like cells, most of which were less than 30 μm in diameter, were observed in adipose tissue.  Proliferating cell nuclear antigen (PCNA) was simultaneously detected in BrdU-labeled nuclei.  Observation of individual mature adipocytes of smeared specimens on glass slides revealed that small sized adipocytes more frequently incorporated BrdU.  Cultured mature adipocytes using the ceiling-cultured method showed clustering of proliferating cells in small-sized adipocytes.  These small cultured adipocytes, but not large ones, extensively incorporated BrdU.  Quantified analysis of BrdU incorporation demonstrated that mature visceral adipocytes, including epididymal, mesenteric and perirenal adipocytes, proliferated more actively than subcutaneous ones.  On the other hand, treatment with pioglitazone (Pio), a ligand of peroxisome proliferator-activated receptor γ, containing food for 2w, elevated BrdU incorporation and expression of PCNA in mature adipocytes isolated from subcutaneous, but not visceral adipose tissue.  Moreover, Pio induced increased BrdU-labeled small-sized subcutaneous adipocytes, which was associated with an increased number of total small adipocytes in subcutaneous adipose tissue.  In conclusion, mature adipocytes have a subgroup representing the potential to replicate, and this proliferation is more active in visceral adipocytes.  Treatment with Pio increases proliferation in subcutaneous adipocytes.  These results may explain the mechanism of Pio-induced hyperplasia especially in subcutaneous adipocytes.
authors.affiliation: Department of General Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kajita
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mori
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hanamoto
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: Kohichiro
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* / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D000077205:Pioglitazone; D061251:Primary Cell Culture / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone