title: A20 reduces lipid storage and inflammation in hypertrophic adipocytes via p38 and Akt signaling.
abstract: Adipose tissue plays a vital role in the development of obesity and related disorders. Our previous study showed that A20, an ubiquitin-editing enzyme with anti-inflammation function, attenuated free fatty acids (FFAs)-induced lipid accumulation in nonalcoholic steatohepatitis. Here, we investigated A20 expression in adipose tissue of obese individuals and its effects on 3T3-L1 lipogenesis as well as the likely mechanisms underlying this process. By re-annotation of raw microarray data downloaded from Gene Expression Omnibus, we found that obese individuals showed significantly higher A20 mRNA levels in adipocytes. In vitro, A20 inhibited MCP-1 and IL-6 secretion in adipocytes. Forced expression of A20 resulted in decreased expression of key markers of lipogenesis and adipogenesis, such as sterol regulatory element binding protein 1c (SREBP-1c) and adipogenesis (aP2), leading to less lipids accumulation in differentiated 3T3-L1 cells. This process was concomitant with attenuated activation of p38 and Akt signaling. Our results suggest that A20 may have therapeutic potential for obesity and related diseases. The mechanisms involved the suppression of lipid storage and inflammation in adipocytes.
authors.affiliation: Department of Health Manage Center, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, No. 160, Pujian Road, Shanghai, China.|Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Luoyan
authors.initials: L
authors.lastname: Ai
authors.affiliation: Department of Health Manage Center, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, No. 160, Pujian Road, Shanghai, China.|The First Hospital of Jiaxing, Jiaxing, Zhejiang, China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Health Manage Center, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, No. 160, Pujian Road, Shanghai, China.|Division of Rheumatology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Health Manage Center, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, No. 160, Pujian Road, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Health Manage Center, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, No. 160, Pujian Road, Shanghai, China.|Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Health Manage Center, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, No. 160, Pujian Road, Shanghai, China.|Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Health Manage Center, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, No. 160, Pujian Road, Shanghai, China.|Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Health Manage Center, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, No. 160, Pujian Road, Shanghai, China.|Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Antao
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Health Manage Center, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, No. 160, Pujian Road, Shanghai, China. zhuping_fan@163.com.
authors.forename: Zhuping
authors.initials: Z
authors.lastname: Fan
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D050155:Lipogenesis; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C513261:Tnfaip3 protein, mouse
keywords: 3T3-L1; A20; Inflammation; Lipogenesis; Obesity