The Lipid Droplet Knowledge Portal: A resource for systematic analyses of lipid droplet biology.

Niklas Mejhert,Dong-Keun Jang,Jason Flannick,Noël P Burtt,Sebastian Boland,Katlyn R Gabriel,Leena Kuruvilla,Jiunn Song,James A Olzmann,Mikael Rydén,Tobias C Walther,Marcin Von Grotthuss,Robert V Farese,Natalie Krahmer,Maria C Costanzo,Chandramohan Chitraju,Scott Frendo-Cumbo

doi:10.1016/j.devcel.2022.01.003

Abstract

Lipid droplets (LDs) are organelles of cellular lipid storage with fundamental roles in energy metabolism and cell membrane homeostasis. There has been an explosion of research into the biology of LDs, in part due to their relevance in diseases of lipid storage, such as atherosclerosis, obesity, type 2 diabetes, and hepatic steatosis. Consequently, there is an increasing need for a resource that combines datasets from systematic analyses of LD biology. Here, we integrate high-confidence, systematically generated human, mouse, and fly data from studies on LDs in the framework of an online platform named the "Lipid Droplet Knowledge Portal" (https://lipiddroplet.org/). This scalable and interactive portal includes comprehensive datasets, across a variety of cell types, for LD biology, including transcriptional profiles of induced lipid storage, organellar proteomics, genome-wide screen phenotypes, and ties to human genetics. This resource is a powerful platform that can be utilized to identify determinants of lipid storage.

Highlights

Lipid droplets (LDs) are phospholipid monolayer-bound organelles found in most eukaryotes and some prokaryotes
We describe the initial version of the LD-Portal and, by highlighting several genes with phenotypes in these datasets that were previously not linked to LDs, we provide examples of how the LD-Portal can be used for discovering new facets of LD biology
The initial datasets integrated in the LD-Portal include a comprehensive dataset for RNA expression in human THP-1 macrophages, LD proteomics for a variety of cell types (Bersuker et al, 2018; Krahmer et al, 2018; Mejhert et al, 2020), and high-content imaging screens of genes governing LD biology in human THP-1 macrophages and Drosophila S2 R+ cells (Mejhert et al, 2020; Song et al, 2021)

Summary

Introduction

Lipid droplets (LDs) are phospholipid monolayer-bound organelles found in most eukaryotes and some prokaryotes. These organelles store neutral lipids, such as triacylglycerols (TGs) and cholesterol esters (CEs), that can be used to generate metabolic energy or cell membranes. Specific proteins, including many important lipid metabolism enzymes (e.g., TG synthesis and degradation enzymes), bind to LD surfaces. Due to their important function in metabolism, alterations in LD biology are causal or implicated in diseases, such as lipodystrophy, atherosclerosis, obesity, and related disorders (e.g., type 2 diabetes [T2D] mellitus, nonalcoholic fatty liver disease [NAFLD], and nonalcoholic steatohepatitis [NASH]). Alterations in LD metabolism are implicated in cancer, neurodegeneration, and immune function (Cruz et al, 2020; Gluchowski et al, 2017; Pereira-Dutra et al, 2019; Seebacher et al, 2020; Walther and Farese, 2012).

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Discussion

Conclusion