title: SUMO-Specific Protease 2 (SENP2) Is an Important Regulator of Fatty Acid Metabolism in Skeletal Muscle.
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-κB-mediated increase in the expression of SENP2. This increase promoted the recruitment of peroxisome proliferator-activated receptor (PPAR)δ and PPARγ, through desumoylation of PPARs, to the promoters of the genes involved in fatty acid oxidation (FAO), such as carnitine-palmitoyl 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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Do
authors.initials: YD
authors.lastname: Koo
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Myungjin
authors.initials: M
authors.lastname: Kim
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Sehyun
authors.initials: S
authors.lastname: Chae
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Byung Yong
authors.initials: BY
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Kim
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Oh
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Seol
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Young-Bum
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea kspark@snu.ac.kr suschung@snu.ac.kr.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Medicine, Seoul National University, Seoul, Korea kspark@snu.ac.kr suschung@snu.ac.kr.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology; D010084:Oxidation-Reduction; D047494:PPAR delta / Q000502:physiology; D047495:PPAR gamma / Q000502:physiology; D019308:Palmitic Acid / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D016328:NF-kappa B; D047494:PPAR delta; D047495:PPAR gamma; D019308:Palmitic Acid; C542591:CPT1B protein, human; D002334:Carnitine O-Palmitoyltransferase; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human; D003066:Coenzyme A Ligases; C583414:ACSL1 protein, human