Lysophosphatidylcholine as an effector of fatty acid-induced insulin resistance

被引：112

作者：

Han, Myoung Sook ^{[2
]}

Lim, Yu-Mi ^{[2
]}

Quan, Wenying ^{[2
]}

Kim, Jung Ran ^{[1
]}

Chung, Kun Wook ^{[2
]}

Kang, Mira ^{[3
]}

Kim, Sunshin ^{[4
]}

Park, Sun Young ^{[2
]}

Han, Joong-Soo ^{[5
,6
]}

Park, Shin-Young ^{[5
,6
]}

Cheon, Hyae Gyeong ^{[1
]}

Rhee, Sang Dal ^{[7
]}

Park, Tae-Sik ^{[1
]}

Lee, Myung-Shik ^{[2
]}

机构：

[1] Gachon Univ Med & Sci, Lee Gil Ya Canc & Diabet Inst, Inchon 406840, South Korea

[2] Sungkyunkwan Univ, Sch Med, Dept Med, Seoul 135710, South Korea

[3] Sungkyunkwan Univ, Sch Med, Ctr Hlth Promot, Samsung Med Ctr, Seoul 135710, South Korea

[4] Korean Natl Canc Ctr, Carcinogenesis Branch, Goyang 410769, South Korea

[5] Hanyang Univ, Inst Biomed Sci, Seoul 133791, South Korea

[6] Hanyang Univ, Dept Biochem & Mol Biol, Coll Med, Seoul 133791, South Korea

[7] Korea Res Inst Chem Technol, Bioorgan Sci Div, Taejon 305343, South Korea

来源：

JOURNAL OF LIPID RESEARCH | 2011年 / 52卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

muscle; lipids; obesity; diabetes; phospholipase A(2); PROTEIN-KINASE-C; SKELETAL-MUSCLE CELLS; KAPPA-B ACTIVATION; TRIGLYCERIDE ACCUMULATION; PANCREATIC-ISLETS; INDUCED APOPTOSIS; BETA-CELLS; PALMITATE; GLUCOSE; MECHANISM;

D O I：

10.1194/jlr.M014787

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The mechanism of FFA-induced insulin resistance is not fully understood. We have searched for effector molecules(s) in FFA-induced insulin resistance. Palmitic acid (PA) but not oleic acid (OA) induced insulin resistance in L6 myotubes through C-Jun N-terminal kinase (JNK) and insulin receptor substrate 1 (IRS-1) Ser307 phosphorylation. Inhibitors of ceramide synthesis did not block insulin resistance by PA. However, inhibition of the conversion of PA to lysophosphatidylcholine (LPC) by calcium-independent phospholipase A(2) (iPLA(2)) inhibitors, such as bromoenol lactone (BEL) or palmitoyl trifluoromethyl ketone (PACOCF(3)), prevented insulin resistance by PA. iPLA(2) inhibitors or iPLA(2) small interfering RNA (siRNA) attenuated JNK or IRS-1 Ser307 phosphorylation by PA. PA treatment increased LPC content, which was reversed by iPLA(2) inhibitors or iPLA(2) siRNA. The intracellular DAG level was increased by iPLA(2) inhibitors, despite ameliorated insulin resistance. Pertussis toxin (PTX), which inhibits LPC action through the G-protein coupled receptor (GPCR)/G alpha(i), reversed insulin resistance by PA. BEL administration ameliorated insulin resistance and diabetes in db/db mice. JNK and IRS-1Ser307 phosphorylation in the liver and muscle of db/db mice was attenuated by BEL. LPC content was increased in the liver and muscle of db/db mice, which was suppressed by BEL. These findings implicate LPC as an important lipid intermediate that links saturated fatty acids to insulin resistance.-Han, M. S., Y-M. Lim, W. Quan, J. R. Kim, K. W. Chung, M. Kang, S. Kim, S. Y. Park, J-S. Han, S-Y. Park, H. G. Cheon, S. D. Rhee, T-S. Park, and M-S. Lee. Lysophosphatidylcholine as an effector of fatty acid-induced insulin resistance. J. Lipid Res. 2011. 52: 1234-1246.

引用

页码：1234 / 1246

页数：13

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