Pref-1, a preadipocyte secreted factor that inhibits adipogenesis.
Preadipocyte factor 1 (Pref-1) belongs to the Notch/Delta/Serrate family of epidermal growth factor-like repeat-containing proteins. Pref-1 is highly expressed in 3T3-L1 cells but is extinguished during adipocyte differentiation. Pref-1 serves as an excellent marker for preadipocytes. Furthermore, Pref-1 is an inhibitor of adipogenesis. Constitutive expression of Pref-1 inhibits, whereas antisense Pref-1 enhances, 3T3-L1 adipocyte differentiation. We found that Pref-1 is synthesized as a transmembrane protein but processed to generate soluble forms, including a large 50-kDa soluble form and the small soluble forms. Furthermore, only the large soluble form, but not the small soluble or the transmembrane forms of Pref-1, is biologically active to inhibit adipogenesis. We recently elucidated that the 50-kDa soluble form of Pref-1 is released by an ADAM family member, tumor necrosis factor-alpha converting enzyme (ADMA 17). In vivo, mice lacking Pref-1 show accelerated fat deposition; conversely, mice overexpressing soluble Pref-1 in adipose tissue show a decrease in fat mass, reduced expression of adipocyte markers, and lower adipocyte-secreted factors. These findings clearly demonstrate the inhibitory effect of Pref-1 on adipogenesis in vivo.
Wang
Yuhui
Y
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Kim
Kyung-Ah
KA
Kim
Jung-Hyun
JH
Sul
Hei Sook
HS
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins