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MetaboLights MTBLS582 - GNPS Global Analyses of Selective Insulin Resistance in Hepatocytes due to Palmitate Lipotoxicity

ABSTRACT: This data set was downloaded from MetaboLights (http://www.ebi.ac.uk/metabolights/) accession number MTBLS582 Abstract:Obesity is tightly linked to hepatic steatosis and insulin resistance. One feature of this association is the paradox of selective insulin resistance: insulin fails to suppress hepatic gluconeogenesis but activates lipid synthesis in the liver. How lipid accumulation interferes selectively with some branches of hepatic insulin signaling is not well understood. Here we provide a resource, based on unbiased approaches and established in a simple cell culture system, to enable investigations of the phenomenon of selective insulin resistance. We analyzed the phosphoproteome of insulin treated human hepatoma cells and identified sites in which palmitate selectively impairs insulin signaling. As an example, we show that palmitate interferes with insulin signaling to FoxO1, a key transcription factor regulating gluconeogenesis, and identify a possible mechanism. This model system, together with our comprehensive characterization of the proteome, phosphoproteome, and lipidome changes in response to palmitate treatment, provides a novel and useful resource for unraveling the mechanisms underlying selective insulin resistance.

INSTRUMENT(S): Exactive (Thermo Scientific)

ORGANISM(S): Homo Sapiens

SUBMITTER: Walther

PROVIDER: MSV000082778 | GNPS | Tue Aug 07 10:50:00 BST 2018

REPOSITORIES: GNPS

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Global Analyses of Selective Insulin Resistance in Hepatocytes due to Palmitate Lipotoxicity

Project description:Obesity is tightly linked to hepatic steatosis and insulin resistance. One feature of this association is the paradox of selective insulin resistance: insulin fails to suppress hepatic gluconeogenesis but activates lipid synthesis in the liver. How lipid accumulation interferes selectively with some branches of hepatic insulin signaling is not well understood. Here we provide a resource, based on unbiased approaches and established in a simple cell culture system, to enable investigations of the phenomenon of selective insulin resistance. We analyzed the phosphoproteome of insulin treated human hepatoma cells and identified sites in which palmitate selectively impairs insulin signaling. As an example, we show that palmitate interferes with insulin signaling to FoxO1, a key transcription factor regulating gluconeogenesis, and identify a possible mechanism. This model system, together with our comprehensive characterization of the proteome, phosphoproteome, and lipidome changes in response to palmitate treatment, provides a novel and useful resource for unraveling the mechanisms underlying selective insulin resistance.

2018-04-26 | MTBLS582 | MetaboLights

Global Analyses of Selective Insulin Resitance in Hepatocytes due to Palmitate Lipotoxicity

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Estrogen signaling and the Metabolic Syndrome: Targeting the hepatic ERalpha action

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