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SUMO-Specific Protease 2 (SENP2) Is an Important Regulator of Fatty Acid Metabolism in Skeletal Muscle

Title
SUMO-Specific Protease 2 (SENP2) Is an Important Regulator of Fatty Acid Metabolism in Skeletal Muscle
Authors
Koo, Young DoChoi, Jin WooKim, MyungjinChae, SehyunAhn, Byung YongKim, MinOh, Byung ChulHwang, Dae HeeSeol, Jae HongKim, Young-BumPark, Young JooChung, Sung SooPark, Kyong Soo
DGIST Authors
Hwang, Dae Hee
Issue Date
2015-07
Citation
Diabetes, 64(7), 2420-2431
Type
Article
Article Type
Article
Keywords
ACTIVATED RECEPTOR-GAMMADIET-INDUCED OBESITYINSULIN-RESISTANCEUNCOUPLING PROTEIN-3PROSTATE-CANCERBETA-OXIDATIONCELLSSUMOYLATIONDEGRADATIONTRANSCRIPTION
ISSN
0012-1797
Abstract
Small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) that reverse protein modification by SUMO are involved in the control of numerous cellular processes, including transcription, cell division, and cancer development. However, the physiological function of SENPs in energy metabolism remains unclear. Here, we investigated the role of SENP2 in fatty acid metabolism in C2C12 myotubes and in vivo. In C2C12 myotubes, treatment with saturated fatty acids, like palmitate, led to nuclear factor-kB- mediated increase in the expression of SENP2. This increase promoted the recruitment of peroxisome proliferator- activated receptor (PPAR)d and PPARg, through desumoylation of PPARs, to the promoters of the genes involved in fatty acid oxidation (FAO), such as carnitinepalmitoyl transferase-1 (CPT1b) and long-chain acyl-CoA synthetase 1 (ACSL1). In addition, SENP2 overexpression substantially increased FAO in C2C12 myotubes. Consistent with the cell culture system, muscle-specific SENP2 overexpression led to a marked increase in the mRNA levels of CPT1b and ACSL1 and thereby in FAO in the skeletal muscle, which ultimately alleviated high-fat diet- induced obesity and insulin resistance. Collectively, these data identify SENP2 as an important regulator of fatty acid metabolism in skeletal muscle and further implicate that muscle SENP2 could be a novel therapeutic target for the treatment of obesity-linked metabolic disorders. © 2015 by the American Diabetes Association.
URI
http://hdl.handle.net/20.500.11750/5812
DOI
10.2337/db15-0115
Publisher
American Diabetes Association
Related Researcher
  • Author Hwang, Daehee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
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Collection:
Department of New BiologySystems Biology and Medicine Lab1. Journal Articles


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