SUMO-specific protease 2 (SENP2) is an important regulator of fatty ac…
doi : 10.2337/db15-0115
Young Do Koo, Jin Woo Choi, Myungjin Kim, Sehyun Chae, Byung Yong Ahn, Min Kim, Byung Chul Oh, Daehee Hwang, Jae Hong Seol, Young-Bum Kim, Young Joo Park, Sung Soo Chung and Kyong Soo Park
Received: 26 January, 2015. Accepted: 27 February, 2015. Published: 17 March, 2015,
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 NFκB-mediated increase in the expression of SENP2. This increase promoted the recruitment of PPARδ 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.