Evidence of mature adipocyte proliferation regulated by proliferin

Abstract

Despite much research, whether mature adipocytes proliferate remains controversial. Here, we examined 5-bromo-2&x2032;-deoxyuridine (BrdU)-labelling of mature adipocytes. Although BrdU incorporation into subcutaneous adipocytes was less than that in visceral adipocytes, pioglitazone (Pio) treatment increased BrdU incorporation in subcutaneous, but not visceral, adipocytes in rats. Fully differentiated 3T3-L1 adipocytes exhibited an increase in cell number and BrdU incorporation with time, with this increase enhanced by Pio treatment. We therefore screened for genes that encode growth factors regulated by Pio, and selected proliferin (PLF). Both gene silencing of PLF by small interfering RNA and treatment with anti-PLF antibody suppressed proliferation in 3T3-L1 adipocytes. In adipocytes isolated from Pio-treated rats, the tissue-specific pattern of PLF expression was similar to that of BrdU incorporation. Administration of an anti-PLF antibody to mice reduced BrdU incorporation into adipocytes. Mature adipocytes thus have the ability to replicate, and this proliferation is positively regulated by PLF.