Perilipin 1 Deficiency Prompts Lipolysis in Lipid Droplets and Aggravates the Pathogenesis of Persistent Immune Activation in Drosophila

Lei Wang; Jiaxin Lin; Kaiyan Yang; Weina Wang; Yan Lv; Xiangkang Zeng; Yaya Zhao; Junjing Yu; Lei Pan

doi:10.1159/000534099

Perilipin 1 Deficiency Prompts Lipolysis in Lipid Droplets and Aggravates the Pathogenesis of Persistent Immune Activation in Drosophila

J Innate Immun. 2023;15(1):697-708. doi: 10.1159/000534099. Epub 2023 Sep 23.

Authors

Lei Wang¹, Jiaxin Lin^{1

2

3}, Kaiyan Yang^{1

2

3}, Weina Wang^{1

2

3}, Yan Lv^{1

4}, Xiangkang Zeng^{1

4}, Yaya Zhao^{1

5}, Junjing Yu⁶, Lei Pan^{1

2

4

5}

Affiliations

¹ Key Laboratory of Molecular Virology and Immunology, The Center for Microbes, Development, and Health, Shanghai Institute of Immunity and Infection (Former Institut Pasteur of Shanghai), Chinese Academy of Sciences, Shanghai, China.
² CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China.
³ University of Chinese Academy of Sciences, Beijing, China.
⁴ Pasteurien College, Soochow University, Suzhou, China.
⁵ The Joint Center for Infection and Immunity between Guangzhou Institute of Pediatrics and Institut Pasteur of Shanghai, Guangzhou Women and Children's Medical Center, Guangzhou, China.
⁶ Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.

Abstract

Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the Drosophila fat body. We find that deficiency of Plin1, a key regulator of LDs' reconfiguration, blocks LDs minimization at the initial stage of immune hyperactivation but enhances LDs breakdown at the later stage of sustained immune activation via recruiting the lipase Brummer (Bmm, homologous to human ATGL). The high wasting in LDs shortens the lifespan of flies with high-energy-cost immune hyperactivation. Therefore, these results suggest a critical function of LDs during long-term immune activation and provide a potential treatment for the resolution of persistent inflammation.

Keywords: Bmm; Immunometabolism; Innate immunity; Lipid droplets; Perilipin 1.

MeSH terms

Animals
Drosophila*
Humans
Lipid Droplets / metabolism
Lipid Metabolism
Lipolysis* / physiology
Perilipin-1 / metabolism

Substances

Perilipin-1

Grants and funding

This work was supported by grants from the National Key Research and Development Program of China (2022YFC2303504), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDPB16), the National Natural Science Foundation of China (92157106, 32270917, 82003361), the Shanghai Municipal Science and Technology Major Project (2019SHZDZX02), and the Shanghai Committee of Science and Technology, China (22ZR1469900).