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PMID: 12588883 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 111 ·No. 4 ·2003-02-00 ·Pages 453-61

Lee K, Villena JA, Moon YS, Kim KH, Lee S, Kang C, Sul HS

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-gamma 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.

MeSH Terms
Adipocytes/cytology,metabolism Animals Base Sequence Bone and Bones/abnormalities,embryology Calcium-Binding Proteins Cell Count Cell Differentiation Cell Size DNA, Complementary/genetics Female Gene Expression Glucose Intolerance/etiology,metabolism Growth Disorders/embryology,genetics Humans Immunoglobulin Fc Fragments/genetics,metabolism Intercellular Signaling Peptides and Proteins Male Membrane Proteins/chemistry,genetics,metabolism Mice Mice, Inbred C57BL Mice, Transgenic Pregnancy Recombinant Fusion Proteins/genetics,metabolism Repressor Proteins/chemistry,genetics,metabolism Solubility
Chemicals
Calcium-Binding Proteins DLK1 protein, human DNA, Complementary Dlk1 protein, mouse Immunoglobulin Fc Fragments Intercellular Signaling Peptides and Proteins Membrane Proteins Recombinant Fusion Proteins Repressor Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lee Kichoon
Department of Nutritional Sciences and Toxicology, and. Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Villena Josep A
Moon Yang Soo
Kim Kee-Hong
Lee Sunjoo
Kang Chulho
Sul Hei Sook
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI15924
Published
2003-02-00
Pages
453-61
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC151920
Subset
IM
Grants
NIDDK NIH HHS · R01 DK050828 · United States
NIDDK NIH HHS · DK-20828 · United States
External Links
PubMed source DOI: 10.1172/JCI15924 PMC Full Text View journal details
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