title: Cold Exposure Induces Proliferation of Mature Brown Adipocyte in a ß3-Adrenergic Receptor-Mediated Pathway.
abstract: Hyperplasia of brown adipose tissue (BAT) is a fundamental mechanism for adaptation to survive in the cold environment in rodents. To determine which cell types comprising BAT contribute to tissue hyperplasia, immunohistochemical analysis using a proliferative marker Ki67 was performed on the BAT from 6-week-old C57BL/6J mice housed at 23°C (control) or 10°C (cold) for 5 days. Interestingly, in the control group, the cell proliferative marker Ki67 was detected in the nuclei of uncoupling protein 1-positive mature brown adipocytes (7.2% ± 0.4% of brown adipocyte), as well as in the non-adipocyte stromal-vascular (SV) cells (19.6% ± 2.3% of SV cells), which include preadiopocytes. The percentage of Ki67-positive brown adipocytes increased to 25.6% ± 1.8% at Day 1 after cold exposure and was significantly higher than the non-cold acclimated control until Day 5 (21.8% ± 1.7%). On the other hand, the percentage of Ki67-positive SV cells gradually increased by a cold exposure and peaked to 42.1% ± 8.3% at Day 5. Injection of a ß3-adrenergic receptor (ß3-AR) agonist for continuous 5 days increased the number of Ki67-positive brown adipocytes even at Day 1 but not that of SV cells. In addition, the ß3-AR antagonist, but not ß1-AR antagonist, attenuated the cold exposure-induced increase in the number of Ki67-positive brown adipocytes. These results suggest that mature brown adipocytes proliferate immediately after cold exposure in a ß3-AR-mediated pathway. Thus, proliferation of mature brown adipocytes as well as preadipocytes in SV cells may contribute to cold exposure-induced BAT hyperplasia.
authors.affiliation: Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Fukano
authors.affiliation: Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamatsu-Ogura
authors.affiliation: Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Tsubota
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo 065-0013, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nio-Kobayashi
authors.affiliation: Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D052437:Adipocytes, Brown / Q000378:metabolism* / Q000502:physiology; D058667:Adrenergic beta-3 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D003080:Cold Temperature; D005786:Gene Expression Regulation; D006965:Hyperplasia / Q000235:genetics; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D019394:Ki-67 Antigen; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3