PXD027332

PXD027332 is an original dataset announced via ProteomeXchange.

Title	Hepatic steatosis contributes to the development of muscle atrophy via inter-organ crosstalk
Description	Individuals with hepatic steatosis often display several metabolic abnormalities including insulin resistance and muscle atrophy. Previously, we found that hepatic steatosis results in an altered hepatokine secretion profile, thereby inducing skeletal muscle insulin resistance via inter-organ crosstalk. In this study, we aimed to investigate whether the altered secretion profile in the state of hepatic steatosis also induces skeletal muscle atrophy via effects on muscle protein turnover. To investigate this, eight-week-old male C57BL/6J mice were fed a chow (4.5% fat) or a high-fat diet (HFD; 45% fat) for 12 weeks to induce hepatic steatosis, after which the livers were excised and cut into ~200 µm slices. Slices were cultured to collect secretion products (conditioned medium; CM). Differentiated L6-GLUT4myc myotubes were incubated with chow or HFD CM to measure glucose uptake. Differentiated C2C12 myotubes were incubated with chow or HFD CM to measure protein synthesis and breakdown, and gene expression via RNA sequencing. Furthermore, proteomics analysis was performed in chow and HFD CM. It was found that HFD CM caused insulin resistance in L6-GLUT4myc myotubes compared with chow CM, as indicated by a blunted insulin-stimulated increase in glucose uptake. Furthermore, protein breakdown was increased in C2C12 cells incubated with HFD CM, while there was no effect on protein synthesis. RNA profiling of C2C12 cells indicated that 197 genes were differentially expressed after incubation with HFD CM, compared with chow CM, and pathway analysis showed that pathways related to anatomical structure and function were enriched. Proteomic analysis of the CM showed that 32 proteins were differentially expressed in HFD CM compared with chow CM. Pathway enrichment analysis indicated that these proteins had important functions with respect to insulin-like Growth Factor transport and uptake, and affect post-translational processes, including protein folding, protein secretion and protein phosphorylation. In conclusion, the results of this study support the hypothesis that secretion products from the liver contribute to the development of muscle atrophy in individuals with hepatic steatosis.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_05:24:24.849.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ruth Meex
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-15 09:29:11	ID requested
⏵ 1	2022-02-17 05:24:25	announced

Pasmans K, Adriaens ME, Olinga P, Langen R, Rensen SS, Schaap FG, Olde Damink SWM, Caiment F, van Loon LJC, Blaak EE, Meex RCR, Inter-Organ Crosstalk. Front Endocrinol (Lausanne), 12():733625(2021) [pubmed]

submitter keyword: Liver steatosis, NAFLD, inter-organ crosstalk, muscle atrophy, insulin resistance, metabolism

Ruth Meex
contact affiliation	Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
contact email	ruth.meex@maastrichtuniversity.nl
lab head
Ruth Meex
contact affiliation	Maastricht University
contact email	ruth.meex@maastrichtuniversity.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027332
     1. Label: PRIDE project
     2. Name: Hepatic steatosis contributes to the development of muscle atrophy via inter-organ crosstalk