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Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver.

Authors
  • Kuriyama, Hiroshi1
  • Liang, Guosheng
  • Engelking, Luke J
  • Horton, Jay D
  • Goldstein, Joseph L
  • Brown, Michael S
  • 1 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Type
Published Article
Journal
Cell Metabolism
Publisher
Elsevier
Publication Date
Jan 01, 2005
Volume
1
Issue
1
Pages
41–51
Identifiers
PMID: 16054043
Source
Medline
Language
English
License
Unknown

Abstract

The escort protein SCAP transports SREBPs from ER to Golgi where the active domains are released to activate genes for fatty acid (FA) and cholesterol synthesis. Mice with conditional SCAP deficiency in liver (L-Scap-) manifest marked reductions in hepatic lipid synthesis. Here, we show that the decreased FA synthesis in liver is balanced by an equal increase in nonhepatic tissues, primarily adipose tissue. Extrahepatic synthesis of FAs preserves adipose mass, even when L-Scap- mice consume a fat-free diet. This compensatory response disappears upon fasting, implicating a role for insulin, the major hormonal activator of FA synthesis. This response is mediated by an insulin-dependent increase in adipocyte SREBP-1c and its target mRNAs. In epididymal fat of L-Scap- mice, phosphorylated Akt, Glut-4 mRNA, and glucose uptake are also increased, indicating insulin hypersensitivity. Plasma VLDL triglycerides are dramatically reduced in L-Scap- mice, underscoring the benefits of synthesizing FAs in fat rather than liver.

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