Abstract

Adipocyte lipid droplets (LDs) play a crucial role in systemic lipid metabolism by storing and releasing lipids to meet the organism's energy needs. Hormonal signals such as catecholamines and insulin act on adipocyte LDs, and impaired responsiveness to these signals can lead to uncontrolled lipolysis, lipotoxicity, and metabolic disease. To investigate the mechanisms that control LD function in human adipocytes, we applied proximity labeling mediated by enhanced ascorbate peroxidase (APEX2) to identify the interactome of PLIN1 in adipocytes differentiated from human mesenchymal progenitor cells. We identified 70 proteins that interact specifically with PLIN1, including PNPLA2 and LIPE, which are the primary effectors of regulated triglyceride hydrolysis, and 4 members of the 14-3-3 protein family (YWHAB, YWHAE, YWHAZ, and YWHAG), which are known to regulate diverse signaling pathways. Functional studies showed that YWHAB is required for maximum cyclic adenosine monophosphate (cAMP)-stimulated lipolysis, as its CRISPR-Cas9-mediated knockout mitigates lipolysis through a mechanism independent of insulin signaling. These findings reveal a new regulatory mechanism operating in human adipocytes that can impact lipolysis and potentially systemic metabolism.

Details

Title
Regulation of lipolysis by 14-3-3 proteins on human adipocyte lipid droplets
Author
Yang, Qin 1   VIAFID ORCID Logo  ; Zinger Yang Loureiro 1   VIAFID ORCID Logo  ; Desai, Anand 1   VIAFID ORCID Logo  ; DeSouza, Tiffany 1   VIAFID ORCID Logo  ; Li, Kaida 1 ; Wang, Hui 1 ; Nicoloro, Sarah M 1 ; Solivan-Rivera, Javier 1 ; Corvera, Silvia 1   VIAFID ORCID Logo 

 Program in Molecular Medicine, University of Massachusetts Chan Medical School , Worcester, MA 01605 , USA 
Publication year
2023
Publication date
Dec 2023
Publisher
Oxford University Press
e-ISSN
27526542
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3191454509
Copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.