In obesity, adipocytes exhibit high metabolic activity accompanied by an increase in lipid mobilization. Recent findings indicate that autophagy plays an important role in metabolic homeostasis. However, the role of this process in adipocytes remains controversial. Therefore, we performed an overall analysis of the expression profiles of 322 lysosomal/autophagic genes in the omental adipose tissue of lean and obese individuals, and found that among 35 significantly differentially expressed genes, 34 genes were upregulated. A large number of lysosomal/autophagic genes also were upregulated in murine 3T3-L1 adipocytes challenged with tumor necrosis factor a (TNF alpha) (within 24 h), which is in accordance with increased autophagy flux in adipocytes. SQSTM1/p62, a selective autophagy receptor that recognizes and binds specifically to ubiquitinated proteins, is transcriptionally upregulated upon TNF alpha stimulation as well. Perilipin 1 (PLIN1), a crucial lipid droplet protein, can be ubiquitinated and interacts with SQSTM1 directly. Thus, TNF alpha-induced autophagy is a more selective process that signals through SQSTM1 and can selectively degrade PLIN1. Our study indicates that local proinflammatory cytokines in obese adipose tissue impair triglyceride storage via autophagy induction.
[1]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6,Dept Endocrinol & Metab, Shanghai Key Clin Ctr Metab Dis,Shanghai Key Lab, Shanghai Inst Diabet,Shanghai Clin Med Ctr Diabet, Shanghai 200233, Peoples R China.
[2]Shanghai Jiao Tong Univ, Sch Med, Inst Endocrine & Metab Dis, Dept Endocrine & Metab Dis,Ruijin Hosp, Shanghai 200025, Peoples R China.
[3]Tongji Univ, Yangpu Hosp, Dept Endocrinol & Metab, Sch Med, Shanghai 200090, Peoples R China.
[4]Qingdao Univ, Dept Endocrinol, Affiliated Hosp, Qingdao 266003, Peoples R China.
[5]Shanghai Univ TCM, Dept Endocrinol, Peoples Hosp 7, Shanghai 200137, Peoples R China.
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