SUMO-specific protease 2 regulates lipid droplet size through ERRα-mediated CIDEA expression in adipocytes

Ji Seon Lee; Jung Eun Min; Hun Jee Choe; Kyong Soo Park; Sung Soo Chung

doi:10.1016/j.bbrc.2023.09.052

SUMO-specific protease 2 regulates lipid droplet size through ERRα-mediated CIDEA expression in adipocytes

Biochem Biophys Res Commun. 2023 Nov 12:681:29-35. doi: 10.1016/j.bbrc.2023.09.052. Epub 2023 Sep 20.

Authors

Ji Seon Lee¹, Jung Eun Min², Hun Jee Choe³, Kyong Soo Park⁴, Sung Soo Chung⁵

Affiliations

¹ Biomedical Research Institute, Seoul National University Hospital, 71 Daehak-ro, Jongno-gu, Seoul, 03282, South Korea.
² Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
³ Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
⁴ Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
⁵ Biomedical Research Institute, Seoul National University Hospital, 71 Daehak-ro, Jongno-gu, Seoul, 03282, South Korea. Electronic address: suschung@snu.ac.kr.

PMID: 37748256
DOI: 10.1016/j.bbrc.2023.09.052

Abstract

Lipid droplets are not only lipid storage sites but also are closely related to lipid metabolism. Lipid droplet growth increases lipid storage capacity and suppresses lipolysis via lipase associated with the lipid droplet surface. The cell death-inducing DFF45-like effector (CIDE) family of proteins mediates lipid droplet fusion, which mainly contributes to lipid droplet growth. We previously demonstrated small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) plays important roles in lipid metabolism and induction/maintenance of adipogenesis. In this study, we determined whether SENP2 regulates lipid droplet size in adipocytes. Overexpression of SENP2 increased lipid droplet size in differentiated 3T3-L1 adipocytes and facilitated CIDEA transcription. We found SENP2 increased CIDEA expression mainly through desumoylation of estrogen-related receptor α (ERRα), which acted in coordination with peroxisome proliferator-activated receptor γ-coactivator α. In addition, palmitate treatment increased SENP2 and CIDEA mRNA levels. Specific small interfering RNA-mediated knockdown of SENP2, as well as ERRα knockdown, eliminated palmitate-induced CIDEA expression. These results suggest SENP2 enhances CIDEA expression by modulating ERRα when SENP2 is upregulated, such as after palmitate treatment, to increase lipid droplet size in adipocytes.

Keywords: Adipocytes; CIDEA; Estrogen-related receptor alpha; Lipid droplets; Sumo-specific protease 2.