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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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Article Development

Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor–1 (Pref-1)

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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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Figure 7

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Reduction in fat pad mass was correlated with the expression levels of P...
Reduction in fat pad mass was correlated with the expression levels of Pref-1/hFc in various transgenic lines. The high expresser line 3AS aP2-Pref-1/hFc showed a 45% reduction in total fad pad weight while lines 2AS aP2-Pref-1/hFc, 21Alb and 4Alb Alb-Pref-1/hFc, which express approximately 50% of that observed in 3AS, exhibited a 27, 21, and 25% reduction in total fat pad weight, respectively.

Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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