Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma

ABSTRACT: Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Notably, LD accumulation is prevented, and tumor burden reduced in vivo upon concurrent inhibition of MYC signaling and glutamine metabolism. Furthermore, we identified the hypoxia inducible lipid droplet associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples, postulated HILPDA as a specific ccRCC biomarker. Together, these discoveries provide an attractive approach for development of new therapeutic interventions for the treatment of this type of renal cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE223069 | GEO | 2024/01/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation

Project description:Neural stem/progenitor cells (NSPCs) generate new neurons throughout adulthood. However, the underlying regulatory processes are still not fully understood. Lipid metabolism plays an important role in regulating NSPC activity: build-up of lipids is crucial for NSPC proliferation, whereas break-down of lipids has been shown to regulate NSPC quiescence. Despite their central role for cellular lipid metabolism, the role of lipid droplets (LDs), the lipid storing organelles, in NSPCs remains underexplored. Here we show that LDs are highly abundant in adult mouse NSPCs, and that LD accumulation is significantly altered upon fate changes such as quiescence and differentiation. NSPC proliferation is influenced by the number of LDs, inhibition of LD build-up, breakdown or usage, and the asymmetric inheritance of LDs during mitosis. Furthermore, high LD-containing NSPCs have increased metabolic activity and capacity, but do not suffer from increased oxidative damage. Together, these data indicate an instructive role for LDs in driving NSPC behaviour.

2021-11-10 | GSE187470 | GEO

Expression data from cultured mouse macrophages isolated from Hilpdaflox/flox (WT) and HilpdaΔMΦ (KO) mice treated with a mixture of fatty acids

Project description:Obesity leads to a state of chronic low-grade inflammation that features accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid droplet accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids. Decreased lipid storage in HILPDA-deficient macrophages could be rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory and metabolic parameters, despite markedly reducing lipid accumulation in macrophages. Overall, we find that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis in macrophages that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Our data question the contribution of lipid droplet accumulation in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.

2019-12-19 | GSE142295 | GEO

Mouse peritoneal macrophages treated with three different fatty acids

2019-12-19 | GSE142294 | GEO

Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma

Project description:Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma

| PRJNA924799 | ENA

Systematic genome perturbation reveals coordination of lipid droplets and metabolic gene regulation

Project description:Lipid droplets (LDs) store lipids for metabolic energy and are central to cellular lipid homeostasis. The mechanisms coordinating lipid storage in LDs with cellular metabolism are unclear but relevant to obesity-related diseases. Here we utilized genome-wide screening to identify genes that modulate lipid storage in human macrophages, a cell type relevant to metabolic diseases. Among ~550 genes regulating lipid storage, we identify MLX, a basic helix-loop-helix leucine-zipper transcription factor that regulates multiple metabolic processes. We show that MLX and family members MLXIP/MondoA and MLXIPL/ChREBP bind LDs via C-terminal amphipathic helices. When LDs increase in cells, LD binding of MLX, MLXIP/MondoA, and MLXIPL/ChREBP reduces their transcriptional activity, whereas the absence of LDs results in hyperactivation. Our findings uncover an unexpected component to a lipid storage response, in which binding of MLX transcription factors to the LD surface modulates their activity, adjusting the expression of metabolic genes to lipid storage levels.

2020-01-01 | GSE126002 | GEO

A fluorescent perilipin 2 knock-in mouse model reveals a high abundance of lipid droplets in the developing and adult brain

Project description:Lipid droplets (LDs) are dynamic lipid storage organelles. They are tightly linked to metabolism and can exert protective functions, making them important players in health and disease. Most LD studies in vivo rely on staining methods, providing only a snapshot. We therefore developed a LD-reporter mouse by endogenously labelling the LD coat protein perilipin 2 (PLIN2) with tdTomato, enabling staining-free fluorescent LD visualisation in living and fixed tissues and cells. Here we validate this model under standard and high-fat diet conditions and demonstrate that LDs are highly abundant in various cell types in the healthy brain, including neurons, astrocytes, ependymal cells, neural stem/progenitor cells and microglia. Furthermore, we also show that LDs are abundant during brain development and can be visualized using live-imaging of embryonic slices. Taken together, our tdTom-Plin2 mouse serves as a novel tool to study LDs and their dynamics under both physiological and diseased conditions in all tissues expressing Plin2.

2024-05-15 | GSE267069 | GEO

Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels

Project description:Type 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid storage exceeds intracellular needs and induces lipotoxic events ultimately contributing to the development of insulin resistance. Lipid droplet (LD)-coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/ADRP) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol storage, marginally increased FA oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet-induced increase of OXPHOS protein content. Diacylglycerol levels were unchanged, while ceramide levels were increased. Despite the increased intramyocellular lipid accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs towards triacylglycerol storage in LDs thereby blunting lipotoxicity-associated insulin resistance. C2C12 cells (mouse myoblast cell line) were treated with fatty acids and effects of knockdown of Perilipin 2 by siRNA were studied by gene expression profiling.

2012-06-08 | E-GEOD-38590 | biostudies-arrayexpress

Proteomic analysis of Metarhizium robertsii Lipid Droplets

Project description:Metarhizium robertsii is one of the model fungus species widely used studying insect-fungus interactions. Our previous studies have shown the accumulation of lipid droplets (LDs) play an essential role in generation of cellular turgor pressure to assist fungal penetration of insect cuticles, and autophagy-related proteins are connected with LD biogenesis and cellular accumulation in M. robertsii. However, full proteomes of LDs are unclear in terms of the species of proteins involved in lipid biosynthesis and degradation. We performed experiments by growing the fungi in different nutrient conditions, isolated the LDs and extracted the LD proteins from the cultures after being grown in a nutrient-rich medium (i.e. Sabouraud dextrose broth, SDB), a minimum medium without nitrogen source (MM-N) and MM-N supplemented with oleate. The protein samples were then subject to LC-MS/MS proteome profilings for identifying and postulating the proteins/pathways involved in lipid metabolisms.

2022-03-01 | PXD001552 | Pride

Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels

2012-06-09 | GSE38590 | GEO

Arabidopsis EARLY RESPONSIVE TO DEHYDRATION 7 associates with lipid droplets via its senescence domain

Project description:Lipid droplets (LDs) are neutral lipid-containing organelles found in all kingdoms of life and are decorated with proteins that carry out a variety of functions. Despite the similar subcellular location, the LD proteins that carry out these functions vary between kingdoms, and only a few LD proteins share obvious amino acid sequence identity between plants and mammals. To better understand the many cellular roles of LDs in plants, a more comprehensive inventory and characterization of LD proteins is required. To this end, we analyzed proteomics data of isolated LDs and identified EARLY RESPONSIVE TO DEHYDRATION 7 (ERD7) as a putative LD protein. mCherry-tagged ERD7 localized to both LDs and to the cytosol when transiently expressed in Nicotiana benthamiana leaves, whereas a fragment of ERD7 containing a “senescence domain” (SD) localized exclusively to LDs with no appreciable accumulation in the cytosol. Similarly, the SDs of the two Arabidopsis ERD7 homologs, here termed SENESCENCE-ASSOCIATED A2 (SENA2) and SENA3, localized exclusively to LDs as did the SD of a phylogenetically distant SD-containing protein, human spartin. In contrast, SDs of the Arabidopsis SENESCENCE-ASSOCIATED B (SENB) family proteins did not localize to LDs and instead localized to mitochondria. Arabidopsis erd7 mutants did not display any observable LD phenotypes in seeds, seedlings or senescent leaves, perhaps due to genetic redundancy of the SENA protein family. A yeast-two-hybrid screen revealed that the S4 family of MYB transcription factors interacts with ERD7, providing a potential avenue for the exploration of ERD7 function. In summary, we here report a previously unappreciated family of plant LD-associated proteins, SENA, which contain SDs that localize to LDs.

2021-03-29 | PXD023047 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data