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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.
Mol Cell Biol. 2007 Jun; 27(12):4317-27.MC

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.

Authors+Show Affiliations

Division of Endocrinology and Metabolism, Department of Developmental Physiology, National Institute for Physiological Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17420279

Citation

Suzuki, Atsushi, et al. "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, pp. 4317-27.
Suzuki A, Okamoto S, Lee S, et al. 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. Mol Cell Biol. 2007;27(12):4317-27.
Suzuki, A., Okamoto, S., Lee, S., Saito, K., Shiuchi, T., & Minokoshi, Y. (2007). 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, 27(12), 4317-27.
Suzuki A, et al. 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. Mol Cell Biol. 2007;27(12):4317-27. PubMed PMID: 17420279.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Suzuki,Atsushi, AU - Okamoto,Shiki, AU - Lee,Suni, AU - Saito,Kumiko, AU - Shiuchi,Tetsuya, AU - Minokoshi,Yasuhiko, Y1 - 2007/04/09/ PY - 2007/4/11/pubmed PY - 2007/7/10/medline PY - 2007/4/11/entrez SP - 4317 EP - 27 JF - Molecular and cellular biology JO - Mol. Cell. Biol. VL - 27 IS - 12 N2 - 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. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/17420279/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_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=17420279 DB - PRIME DP - Unbound Medicine ER -