Obesity-associated inflammation triggers an autophagy–lysosomal response in adipocytes and causes degradation of perilipin 1

• Published in: Cell death & disease 2019-02, Vol.10 (2), p.121-121, Article 121
• Main Authors: Ju, Liping, Han, Junfeng, Zhang, Xiaoyan, Deng, Yujie, Yan, Han, Wang, Congrong, Li, Xiaohua, Chen, Shuqin, Alimujiang, Miriayi, Li, Xu, Fang, Qichen, Yang, Ying, Jia, Weiping
• Format: Article
• Language: English
• Subjects: 101/28; 38/91; 3T3-L1 Cells; 64/60; 692/163/2743/393; 692/699/2743/393; 82/80; Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Adipose tissue; Animals; Antibodies; Autophagy; Autophagy - drug effects; Biochemistry; Biomedical and Life Sciences; Cathepsin B - antagonists & inhibitors; Cathepsin B - metabolism; Cell Biology; Cell Culture; Culture Media, Conditioned - pharmacology; Homeostasis; Humans; Immunology; Inflammation; Inflammation - etiology; Inflammation - metabolism; Inflammation - pathology; Life Sciences; Lysosomes - metabolism; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Male; Metabolism; Mice; Mice, Inbred C57BL; Obesity; Obesity - complications; Obesity - pathology; Palmitates - pharmacology; Perilipin-1 - genetics; Perilipin-1 - metabolism; Phagocytosis; Sequestosome-1 Protein - genetics; Sequestosome-1 Protein - metabolism; Transcription; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α; Ubiquitination - drug effects; Up-Regulation - drug effects
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1393-8

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 α (TNFα) (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 TNFα stimulation as well. Perilipin 1 (PLIN1), a crucial lipid droplet protein, can be ubiquitinated and interacts with SQSTM1 directly. Thus, TNFα-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.