Dataset Information

Untargeted Lipidomics of Liver and Plasma of Plin4 Knockout and Wild-Type Mice Fed Control or Western Diet

ABSTRACT: This study investigates the impact of Plin4 gene deletion on lipid metabolism in mouse liver and plasma under different dietary conditions using untargeted lipidomics. Female wild-type (Plin4+/+) and knockout (Plin4-/-) mice were fed either a control diet or a Western diet high in fat, fructose, and cholesterol. Samples included liver tissue and plasma (n = 5 per tissue type per group, total n = 40). Lipids were extracted using isopropanol, with pooled quality control samples prepared and injected regularly for signal correction. Lipidomic analysis was performed using ultra-high-performance liquid chromatography coupled to Orbitrap mass spectrometry (UHPLC-MS), with data acquired using Xcalibur and processed in Compound Discoverer and LipidSearch. Features were normalized using the SERRF algorithm, and lipid identifications were based on MS/MS fragmentation matching. This dataset provides global lipid profiles for evaluating the metabolic effects of Plin4 deletion in both normal and diet-induced obese states.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Knut Tomas Dalen

PROVIDER: MSV000099281 | MassIVE |

REPOSITORIES: MassIVE

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Publications

Elevated adipose inflammation, but reduced hepatic triacylglycerol storage in diet-induced obese Plin4<sup>-/-</sup> mice.

Doncheva Atanaska Ivanova AI Higa Ryoko R Khanal Prabhat P Øksenvåg Ingebrigtsen Martine Villemo MV Li Yuchuan Y Kolan Shrikant S Kolan Pratibha P Kvasnicka Ales A Jermstad Ingunn I Khan Shaista S Skålhegg Bjørn Steen BS Kolset Svein Olav SO Nebb Hilde H Hjorth Marit M Norheim Frode Amador FA Dalen Knut Tomas KT

The Journal of biological chemistry 20251212

Plin4 is transcriptionally regulated by peroxisome proliferator-activated receptor gamma and is primarily expressed in white adipose tissue (WAT). We found that expression of Plin4 is elevated in the liver upon prolonged feeding with an obesogenic diet containing saturated fat, fructose, and cholesterol (Western diet). To investigate the functional role of Plin4 in energy metabolism, we generated Plin4<sup>-/-</sup> mice and assessed effects upon Plin4 removal in the liver, WAT, and skeletal mus ...[more]

PMID: 41391763

Similar Datasets

Project description:The sterol regulatory element binding proteins (SREBPs) are transcription factors that govern cholesterol and fatty acid metabolism. Owing to their central role in controlling hepatic lipid and lipoprotein metabolism their activity is tightly coordinated, and accordingly dysregulation of the SREBP pathway is associated with development of dyslipidemia and non-alcoholic fatty liver disease. Using a suite of genome-wide genetic screens we have recently identified SPRING (C12ORF49) as a novel post-transcriptional regulator of SREBP activation in vitro. Our previous work demonstrated that constitutive ablation of Spring in mice is embryonically lethal. Here we show that inducible global deletion of Spring is also untolerated, and therefore to interrogate the physiological role of SPRING in controlling hepatic lipid metabolism we developed liver-specific Spring knockout mice (LKO). Liver transcriptomics and proteomics analysis revealed severely attenuated SREBP signaling in livers and in hepatocytes of LKO mice, which was associated with marked effects on both plasma and hepatic lipid levels. In plasma, total cholesterol levels were dramatically reduced in both male and female LKO mice, apparent in both the LDL and HDL fractions, while triglyceride levels remained largely unaffected. In liver, loss of Spring diminished cholesterol and triglyceride biosynthesis resulting in decreased hepatic cholesterol and triglyceride content. This coincided with reduced secretion of VLDL into the circulation. Consistent with diminished hepatic de novo lipogenesis, LKO mice were protected from developing hepatosteatosis when challenged with a fructose-rich diet. Supporting the significance of our findings in mice, we identified common and rare SPRING genetic variants that are strongly associated with circulating HDL-c and ApoA1 levels in humans. Collectively, our study positions SPRING as a core component of hepatic SREBP signaling, and consequently of systemic lipid metabolism in mice and humans.

Dataset Information

Untargeted Lipidomics of Liver and Plasma of Plin4 Knockout and Wild-Type Mice Fed Control or Western Diet

Dataset's files

Publications

Elevated adipose inflammation, but reduced hepatic triacylglycerol storage in diet-induced obese Plin4<sup>-/-</sup> mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Untargeted Lipidomics of Liver and Plasma of Plin4 Knockout and Wild-Type Mice Fed Control or Western Diet

Dataset's files

Publications

Elevated adipose inflammation, but reduced hepatic triacylglycerol storage in diet-induced obese Plin4&lt;sup&gt;-/-&lt;/sup&gt; mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Elevated adipose inflammation, but reduced hepatic triacylglycerol storage in diet-induced obese Plin4<sup>-/-</sup> mice.