Dataset Information

Mouse purified hepatocyte secretome iTRAQ LC/MS

ABSTRACT: This study tests whether hepatic steatosis, independent of inflammation, alters the hepatocyte protein secretory profile, and examines whether changes in the secretory products contribute to the development of metabolic dysfunction in other cell types. Mouse hepatocytes were isolated by flow cytometry and cultured in serum-free conditions. Conditioned media was used for LC/MS analysis to compare hepatocytes from chow fed animals to high-fat diet animals with liver steatosis.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Christoph Krisp

LAB HEAD: Matthew Watt

PROVIDER: PXD002858 | Pride | 2018-03-14

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Proj12426_8plex_SCX_All.group	Other
	Proj12426_8plex_SCX_All.xml	Xml
	Proj12426_iTRAQ8plex-SCX_F01.wiff	Wiff
	Proj12426_iTRAQ8plex-SCX_F01.wiff.mtd	Wiff
	Proj12426_iTRAQ8plex-SCX_F01.wiff.scan	Wiff

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Publications

Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism.

Meex Ruth C RC Hoy Andrew J AJ Morris Alexander A Brown Russell D RD Lo Jennifer C Y JC Burke Melissa M Goode Robert J A RJ Kingwell Bronwyn A BA Kraakman Michael J MJ Febbraio Mark A MA Greve Jan Willem JW Rensen Sander S SS Molloy Mark P MP Lancaster Graeme I GI Bruce Clinton R CR Watt Matthew J MJ

Cell metabolism 20151022 6

Liver steatosis is associated with the development of insulin resistance and the pathogenesis of type 2 diabetes. We tested the hypothesis that protein signals originating from steatotic hepatocytes communicate with other cells to modulate metabolic phenotypes. We show that the secreted factors from steatotic hepatocytes induce pro-inflammatory signaling and insulin resistance in cultured cells. Next, we identified 168 hepatokines, of which 32 were differentially secreted in steatotic versus non ...[more]

PMID: 26603189

Similar Datasets

Project description:Recent studies have reported that glycosphingolipids (GSL) might be involved in obesity induced insulin resistance. Those reports suggested that inhibition of GSL biosynthesis in animals ameliorated insulin sensitivity accompanied with improved glycemic control leading to decreased liver steatosis in obese mice. In addition, GSL depletion altered hepatic secretory function. In those studies, ubiquitously acting inhibitors for GSL-biosynthesis have been used to inhibit function of the enzyme Ugcg (UDP-glucose:ceramide glucosyltransferase), catalyzing the first step of the glucosylceramide based GSL-synthesis pathway. In the present study, a genetic approach for GSL deletion in hepatocytes was chosen to achieve full inhibition of GSL synthesis and to prevent possible adverse effects caused by Ugcg-inhibitors. Using the Cre/loxP system under control of the albumin promoter, GSL biosynthesis in hepatocytes and their release into the plasma could be effectively blocked. Deletion of GSL in hepatocytes did not change quantity of bile excretion through the biliary duct. Total bile salt content in bile-, feces- and plasma from mutant mice showed no difference as compared to control animals. Cholesterol concentration in liver-, bile-, feces- and plasma-samples remained unaffected. Lipoprotein concentration in plasma-samples in mutant animals reached similar levels as in their control littermates. No alteration in glucose tolerance after intraperitoneal application of glucose and insulin appeared in mutant animals. A preventive effect of GSL-deficiency on development of liver steatosis after high fat diet feeding could not be observed. Conclusion: The data suggest that GSL in hepatocytes are not essential for sterol, glucose and lipoprotein metabolism and do not prevent high fat diet-induced liver steatosis, indicating that Ugcg inhibitors exert their effect on hepatocytes either independently of GSL or mediated by other (liver) cell types. Comparison of wildtype mouse liver function versus Ugcg-deficient