TY - JOUR
T1 - Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver
AU - Kuriyama, Hiroshi
AU - Liang, Guosheng
AU - Engelking, Luke J.
AU - Horton, Jay D.
AU - Goldstein, Joseph L.
AU - Brown, Michael S.
N1 - Funding Information:
We thank our colleagues Kiyosumi Takaishi and Young-Ah Moon at UT Southwestern Medical Center and Yoshihiro Tochino at Osaka University for helpful advice on experiments, Scott Clark and Jeff Cormier for excellent technical assistance, and Monica Mendoza and Richard Gibson for invaluable help with animals. This research was supported by grants from NIH (HL20948), Perot Family Foundation, Moss Heart Fund, and W.M. Keck Foundation. L.J.E. was supported by NIH Medical Scientist Training Grant GM-08014.
PY - 2005/1
Y1 - 2005/1
N2 - 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.
AB - 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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U2 - 10.1016/j.cmet.2004.11.004
DO - 10.1016/j.cmet.2004.11.004
M3 - Article
C2 - 16054043
AN - SCOPUS:24344490326
SN - 1550-4131
VL - 1
SP - 41
EP - 51
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -