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PMID: 17420279 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor alpha gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the alpha2 form of AMP-activated protein kinase.

Molecular and cellular biology ·Vol. 27 ·No. 12 ·2007-06-00 ·Pages 4317-27

Suzuki A, Okamoto S, Lee S, Saito K, Shiuchi T, Minokoshi Y

Abstract

Leptin stimulates fatty acid oxidation in skeletal muscle through the activation of AMP-activated protein kinase (AMPK) and the induction of gene expression, such as that for peroxisome proliferator-activated receptor alpha (PPARalpha). We now show that leptin stimulates fatty acid oxidation and PPARalpha gene expression in the C2C12 muscle cell line through the activation of AMPK containing the alpha2 subunit (alpha2AMPK) and through changes in the subcellular localization of this enzyme. Activated alpha2AMPK containing the beta1 subunit was shown to be retained in the cytoplasm, where it phosphorylated acetyl coenzyme A carboxylase and thereby stimulated fatty acid oxidation. In contrast, alpha2AMPK containing the beta2 subunit transiently increased fatty acid oxidation but underwent rapid translocation to the nucleus, where it induced PPARalpha gene transcription. A nuclear localization signal and Thr(172) phosphorylation of alpha2 were found to be essential for nuclear translocation of alpha2AMPK, whereas the myristoylation of beta1 anchors alpha2AMPK in the cytoplasm. The prevention of alpha2AMPK activation and the change in its subcellular localization inhibited the metabolic effects of leptin. Our data thus suggest that the activation of and changes in the subcellular localization of alpha2AMPK are required for leptin-induced stimulation of fatty acid oxidation and PPARalpha gene expression in muscle cells.

MeSH Terms
3T3-L1 Cells AMP-Activated Protein Kinases Amino Acid Sequence Animals Cell Line, Tumor Cell Nucleus/metabolism Cells, Cultured Cytoplasm/metabolism Enzyme Activation/drug effects Fatty Acids/metabolism Gene Expression Leptin/administration & dosage,pharmacology,physiology Mice Models, Biological Molecular Sequence Data Multienzyme Complexes/chemistry,metabolism Muscle, Skeletal/cytology,metabolism Myoblasts/cytology,drug effects,metabolism Neoplasms, Muscle Tissue/pathology Nuclear Localization Signals Oxidation-Reduction PPAR alpha/metabolism Protein Serine-Threonine Kinases/chemistry,metabolism Protein Subunits/chemistry,metabolism Time Factors Transcription, Genetic/drug effects
Chemicals
Fatty Acids Leptin Multienzyme Complexes Nuclear Localization Signals PPAR alpha Protein Subunits Protein Serine-Threonine Kinases AMP-Activated Protein Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Suzuki Atsushi
Division of Endocrinology and Metabolism, Department of Developmental Physiology, National Institute for Physiological Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi, Japan.
Okamoto Shiki
Lee Suni
Saito Kumiko
Shiuchi Tetsuya
Minokoshi Yasuhiko
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.02222-06
Published
2007-06-00
Epub
2007-00-09
Pages
4317-27
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1900064
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.02222-06 PMC Full Text View journal details
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