Leptin Stimulates Fatty Acid Oxidation and Peroxisome Proliferator-Activated Receptor α Gene Expression in Mouse C2C12 Myoblasts by Changing the Subcellular Localization of the α2 Form of AMP-Activated Protein Kinase

• DOI: 10.1128/mcb.02222-06
• Publication Date: 2007-04-10T00:35:59Z
• Authors: Atsushi Suzuki; Shiki Okamoto; Suni Lee; Kumiko Saito; Tetsuya Shiuchi; Yasuhiko Minokoshi
• Keywords: Acetyl-CoA Carboxylase

AbstractLeptin stimulates fatty acid oxidation in skeletal muscle through the activation of AMP-activated protein kinase (AMPK) and induction gene expression, such as that for peroxisome proliferator-activated receptor α (PPARα). We now show leptin PPARα expression C2C12 cell line AMPK containing α2 subunit (α2AMPK) changes subcellular localization this enzyme. Activated α2AMPK β1 was shown to be retained cytoplasm, where it phosphorylated acetyl coenzyme A carboxylase thereby stimulated oxidation. In contrast, β2 transiently increased but underwent rapid translocation nucleus, induced transcription. nuclear signal Thr172 phosphorylation were found essential α2AMPK, whereas myristoylation anchors cytoplasm. The prevention change its inhibited metabolic effects leptin. Our data thus suggest are required leptin-induced stimulation cells. SUPPLEMENTAL MATERIALThis work supported by a Grant-in-Aid Scientific Research (B) (16390062) (to Y.M.), Exploratory (17659069) Young Scientists (A) (18689023) A.S.), (18790629) S.O.) from Ministry Education, Culture, Sports, Science, Technology Japan; research award Diko Foundation Y.M.); Smoking Japan Applied Enzymology Y.M.).We thank H. Esumi T. Ogura plasmids, K. Kameda (Ehime University, Japan) constitutively active form α1 used positive control activity assay, Center Analytical Instruments at National Institute Basic Biology (Okazaki) DNA sequencing.