RRC ID |
38200
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Author |
Takahashi K, Sasabe N, Ohshima K, Kitazato K, Kato R, Masuda Y, Tsurumaki M, Obama T, Okudaira S, Aoki J, Arai H, Yamaguchi T, Itabe H.
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Title |
Glucagon regulates intracellular distribution of adipose differentiation-related protein during triacylglycerol accumulation in the liver.
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Journal |
J Lipid Res
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Abstract |
Cellular lipid droplets (LD) are organelles involved in cellular lipid metabolism. When liver cellular components were fractionated using sucrose density gradient centrifugation, adipose differentiation-related protein (ADRP) was distributed in both the top and bottom fractions, which correspond to the LD and membranous fractions, respectively, in the mouse liver under normal feeding conditions. After overnight fasting, triacylglycerol and ADRP increased nearly 2.5-fold in the mouse liver, and a portion appeared in the intermediate-density LD (iLD) fractions. ADRP in the iLD fractions was also increased in a mouse nonalcoholic steatohepatitis model induced by methione/choline-deficient diet. When HuH-7 human hepatoma cells were incubated with oleic acid for 24 h, the amount of ADRP increased, and it was distributed in both the LD and membrane fractions. However, ADRP appeared in the iLD fractions upon treatment of HuH-7 cells with glucagon. This behavior of ADRP was cAMP-dependent, as the ADRP-positive iLD fractions were induced by dibutylyl cAMP and were blocked by protein kinase A inhibitors. A portion of ADRP colocalized microscopically with calnexin, which is present in the iLD fractions, by treatment of HuH-7 cells or human primary hepatocytes with oleic acid and glucagon, but not by treatment with oleic acid alone. Glucagon has a role in the reorganization of endoplasmic reticulum membranes to generate ADRP-associated lipid-poor particles in hepatic cells, which is related to LD formation during lipid storage.
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Volume |
51(9)
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Pages |
2571-80
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Published |
2010-9-1
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DOI |
10.1194/jlr.M004648
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PII |
S0022-2275(20)42287-4
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PMID |
20529882
|
PMC |
PMC2918440
|
MeSH |
Animals
Cell Line
Glucagon / metabolism*
Hepatocytes / cytology
Hepatocytes / metabolism
Humans
Lipid Metabolism / physiology
Liver / cytology
Liver / metabolism*
Male
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mice
Mice, Inbred C57BL
Perilipin-2
Signal Transduction / physiology
Triglycerides / metabolism*
|
IF |
4.483
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Times Cited |
10
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WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
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Resource |
Human and Animal Cells |
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