Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor–1 (Pref-1)
Kichoon Lee, … , Chulho Kang, Hei Sook Sul
Kichoon Lee, … , Chulho Kang, Hei Sook Sul
Published February 15, 2003
Citation Information: J Clin Invest. 2003;111(4):453-461. https://doi.org/10.1172/JCI15924.
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Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor–1 (Pref-1)

Abstract

Preadipocyte factor-1 (Pref-1) is a transmembrane protein highly expressed in preadipocytes. Pref-1 expression is, however, completely abolished in adipocytes. The extracellular domain of Pref-1 undergoes two proteolytic cleavage events that generate 50 and 25 kDa soluble products. To understand the function of Pref-1, we generated transgenic mice that express the full ectodomain corresponding to the large cleavage product of Pref-1 fused to human immunoglobulin-γ constant region. Mice expressing the Pref-1/hFc transgene in adipose tissue, driven by the adipocyte fatty acid–binding protein (aP2, also known as aFABP) promoter, showed a substantial decrease in total fat pad weight. Moreover, adipose tissue from transgenic mice showed reduced expression of adipocyte markers and adipocyte-secreted factors, including leptin and adiponectin, whereas the preadipocyte marker Pref-1 was increased. Pref-1 transgenic mice with a substantial, but not complete, loss of adipose tissue exhibited hypertriglyceridemia, impaired glucose tolerance, and decreased insulin sensitivity. Mice expressing the Pref-1/hFc transgene exclusively in liver under the control of the albumin promoter also showed a decrease in adipose mass and adipocyte marker expression, suggesting an endocrine mode of action of Pref-1. These findings demonstrate the inhibition of adipogenesis by Pref-1 in vivo and the resulting impairment of adipocyte function that leads to the development of metabolic abnormalities.

Authors

Kichoon Lee, Josep A. Villena, Yang Soo Moon, Kee-Hong Kim, Sunjoo Lee, Chulho Kang, Hei Sook Sul

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Growth retardation and bone malformation in aP2-Pref-1/hFc transgenic mi...
Growth retardation and bone malformation in aP2-Pref-1/hFc transgenic mice. (a) Pref-1 expression in aP2-Pref-1/hFc embryos. Total protein extracts from embryo day 12 (E12) embryo from wild-type and 3AS line were subjected to Western blot analysis for Pref-1. Pref-1/hFc fusion protein was detected as a 75-kDa band only in transgenic embryo, while multiple forms of endogenous Pref-1 were detected at around 50-kDa in both wild-type and transgenic mice. (b) The appearances of wild-type and aP2-Pref-1/hFc transgenic littermates were compared at E18, showing the growth retardation of transgenic embryos. (c) The transgenic mice had kinky tails, the severity of which is correlated with levels of transgene expression. (d) Bone and cartilage staining. Embryos (E17) were stained with alizarin red for bone and alcian blue for cartilages. The Pref-1/hFc transgenic embryos had a smaller thoracic cavity with short ribs. Vertebrae were fused and disorganized, resulting in scoliosis.